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Hypoalbuminemia

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Arthus reaction

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Pattern recognition receptor

C3a (complement)

Anafilatoksin

Complement component 4

Classical complement pathway

Alternative complement pathway

Complement membrane attack complex

Cryoglobulinemia

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Complement system

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Receptors33

• The present studies were undertaken to determine whether neuronal subsets in normal brains constitutively express functionally competent C5a receptors. (jimmunol.org)
• In situ hybridization studies coupled with immunohistochemical approaches revealed that most neurons in the hippocampal formation, many pyramidal cortical neurons, and cerebellar Purkinje neurons in normal human and murine brains constitutively express C5a receptors. (jimmunol.org)
• Neuronal C5a receptors bound C5a-coated fluorescent microspheres, and primary rodent hippocampal neurons responded to C5a with increased calcium fluxes via a pertussis-sensitive, presumably Gi-coupled protein. (jimmunol.org)
• Additional studies with human neuroblastoma cells conducted to address the functional role of C5a receptors revealed that C5a triggered rapid activation of protein kinase C and activation and nuclear translocation of the NF-κB transcription factor. (jimmunol.org)
• Thus, normal rodent hippocampal neurons as well as undifferentiated and differentiated human neuroblastoma cells express functional C5a receptors. (jimmunol.org)
• Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. (molvis.org)
• Retinal Iba1-positive microglia/macrophages express receptors for C3a and C5a. (molvis.org)
• These divergent properties of complement anaphylatoxins in the light damage model provide a rationale for testing the differential effects of these receptors in additional retinal and neurodegeneration models. (molvis.org)
• Human RPE/choroid was assayed for the presence of C3a and C5a receptors (C3aR and C5aR) using RT-PCR and immunohistochemistry. (arvojournals.org)
• Based on the evidence that neuronal death in response to excitotoxic insult involves the regulation of GluR2 receptor expression [ 16 ] and that GluR2 receptor expression is reduced coincidental to increase in expression of apoptotic markers like caspase 3 in Alzheimer's brain [ 17 ] we decided to explore the role of GluR2 receptors in C5a mediated protection in vivo and in vitro . (biomedcentral.com)
• Complement C5a Receptors , Placental Inflammation and Reproductive Impairment. (edu.au)
• C5a modulates balance between activating versus inhibitory IgG Fc receptors on leukocytes, thereby enhancing autoimmune response. (acrobiosystems.com)
• The complement system exerts many of its effects through complement receptors (CRs). (medscape.com)
• Of the 8 plasma membrane receptors for complement, only deficiencies of CR3 and CR4 due to CD18 deficiency have been described, known as leukocyte adhesion deficiency (LAD) type 1 . (medscape.com)
• [ 6 ] These receptors play a role in C3a-mediated and C5a-mediated anaphylactic reactions. (medscape.com)
• enhance G-CSF creation in civilizations of PEMs from either C5L2-lacking or C5aR-deficient mice, indicating that both C5a receptors are essential for mediating the consequences of C5a in creation of G-CSF. (bio-zentrum.com)
• The complement system as understood today is a multimolecular system composed of more than 32 proteins and consisting of serum proteins, serosal proteins, and cell membrane receptors that bind to complement fragments. (medscape.com)
• The complement system consists of 7 serum and 9 membrane regulatory proteins, 1 serosal regulatory protein, and 8 cell membrane receptors that bind complement fragments. (medscape.com)
• The complement anaphylatoxin, C5a, through binding to its receptors (C5aR or C5L2), has important biological properties for recruitment and activation of phagocytes. (frontiersin.org)
• The contributions of C5a interaction with its receptors in the production of IL-17/IL-23 and promotion of IL-17-dependent immune responses are reviewed. (frontiersin.org)
• The effects of its products on complement receptors of immune and phagocytic cells are equally diverse. (frontiersin.org)
• C5a is an anaphylatoxin and also has the ability to act as an activator and chemoattractant for phagocytes by binding to its receptors, C5aR and C5L2. (frontiersin.org)
• The complement system is one of the major contributors to innate immunity and contains a series of soluble and cell surface proteins, including plasma components, specific receptors and diverse regulators. (nature.com)
• C3 inhibition could simultaneously block C3a and C5a generation, as well as intrapulmonary C3 activation and IL-6 release from alveolar macrophages, or other cells that express C3a receptors (C3aRs) and/or C5a receptors (C5aRs), thereby ameliorating lung injury. (nature.com)
• Complement receptors in neutrophils. (wikipedia.org)
• 1992). "Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19. (wikipedia.org)
• 1998). "Expression of receptors for C5a anaphylatoxin (CD88) on human bronchial epithelial cells: enhancement of C5a-mediated release of IL-8 upon exposure to cigarette smoke. (wikipedia.org)
• The data support the need for further efficacy testing of targeting complement and/or its receptors to improve kidney transplant outcome in humans. (jci.org)
• Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair. (upenn.edu)
• Complement-activation fragment C4a mediates effector functions by binding as untethered agonist to protease-activated receptors 1 and 4. (upenn.edu)
• Over 30 proteins and protein fragments make up the complement system, including serum proteins , and cell membrane receptors . (wikipedia.org)
• It works by inhibiting C5a receptors in leukocytes, including neutrophils. (thefreedictionary.com)
• C5a (C3a, C4a) act on specific receptors to produce similar local inflammatory responses (anaphylatoxins). (slideserve.com)

C5aR27

• C5a binds to a signaling G-protein coupled receptor (C5aR/CD88) and a non-signaling GPCR termed C5L2. (rndsystems.com)
• In addition, C5a was found to be mitogenic for undifferentiated human neuroblastoma cells, a novel action for the C5aR. (jimmunol.org)
• The myeloid receptor for C5a (C5aR, CD88), a member of the rhodopsin superfamily, binds C5a with high affinity ( K d = 1.4 nM) ( 3 , 4 ). (jimmunol.org)
• C5a is the only known natural ligand for the C5aR. (jimmunol.org)
• Constitutive expression of the C5aR on nonmyeloid cells suggests as yet undetermined noninflammatory roles for C5a. (jimmunol.org)
• We assessed the effect of anaphylatoxin C3a receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced migration of microglia/macrophages into the mouse outer retina via immunofluorescence and real-time quantitative PCR. (molvis.org)
• We found that the mRNA levels of C3, C5, C3aR, C5aR, and two activators of the complement alternative pathway, Cfb and Cfd, were all upregulated after light exposure. (molvis.org)
• Here, we seek to elucidate the relationship between complement anaphylatoxins and microglia in the light damage model using C3aR and C5aR KO mice. (molvis.org)
• In this study, we found that intestinal IR induced ALI-like symptoms, and C5a receptor (C5aR) expression was upregulated in alveolar macrophages, which are resident macrophages in lung tissue and are important in pulmonary homeostasis. (nih.gov)
• C5a produced during lung injury binds to C5aR in alveolar macrophages, initiates downstream signaling that promotes autophagy, leading to apoptosis of alveolar macrophages. (nih.gov)
• Using Mφ-ATG5(-/-) mice, in which the atg5 is deficient specifically in macrophages and autophagy is inhibited, we confirmed that in vivo C5a interacting with C5aR induced autophagy in alveolar macrophages, which promoted alveolar macrophage apoptosis. (nih.gov)
• C5a binds to its G protein-coupled receptor (C5aR) on polymorphonuclear leukocytes (PMNLs) through a high-affinity helical bundle and a low-affinity C terminus, the latter being solely responsible for receptor activation. (aspetjournals.org)
• We have hypothesized that a turn conformation is important for activity of the C terminus of C5a and herein report small cyclic peptides that are stable turn mimics with potent antagonism at C5aR on human PMNLs. (aspetjournals.org)
• Competition between a cyclic antagonist and either C5a or an acyclic agonist for C5aR on PMNLs supports a common or overlapping binding site on the C5aR. (aspetjournals.org)
• Alternatively, C5L2 may affect C5a function through formation of a heteromeric complex with the C5aR, or it may utilize a G protein-independent signaling pathway. (elsevier.com)
• Upon agonist binding, the C5a anaphylatoxin receptor (C5aR) is rapidly phosphorylated on phosphorylation sites that are located within the C-terminal domain of the receptor. (jpt.com)
• In differentiated U937 cells, which endogenously express C5aR, stimulation with low C5a concentrations resulted in a very rapid (t((1/2)) approximately 20 s), albeit transient, receptor phosphorylation. (jpt.com)
• Both C5a and C5adesArg (with much lower affinity) are ligands for the G-protein coupled C5aR receptor(CD88) [2, 3]. (bio-zentrum.com)
• In polymorphonuclear leukocytes (PMNs) and macrophages, ligation of C5a with the C5aR receptor leads to rapid buildup of cytosolic Ca2+, activation of MAPK signaling pathways, chemotaxis, respiratory burst, release of toxic granules and regulation of cytokine expression [2, 3, 7]. (bio-zentrum.com)
• Using C5a, C5aR, or C5L2 deficiency or blockade, IL-17/IL-23 production and/or IL-17-dependent disease progression has been shown to be substantially modified. (frontiersin.org)
• Based on the structure-activity study of the COOH-terminal domain of C5a, peptide agonists with varied C5aR affinities and diverse selectivity to cells expressing C5aR were synthesized ( 5 ). (aacrjournals.org)
• C5 inhibitors have been safely used in the clinic for almost 15 years, and their use in initial clinical trials is supported by the well-established role of the C5a-C5aR axis in the pathophysiology of ARDS. (nature.com)
• Antibody blockade of C5a or C5a receptor (C5aR) rescued susceptible mice from CM. In vitro studies showed that C5a-potentiated cytokine secretion induced by the malaria product P. falciparum glycosylphosphatidylinositol and C5aR blockade abrogated these amplified responses. (rupress.org)
• Blockade of C5a activity or C5aR with antibodies or C5aR antagonists in animal models of sepsis prevents multiorgan injury and improves survival ( 19 , 21 - 24 ). (rupress.org)
• We further demonstrate that deficiency of C5a-like receptor (C5L2) has the reverse effect of C5aR/CD88 deficiency and results in more severe disease, indicating that C5aR/CD88 engagement enhances inflammation and C5L2 engagement suppresses inflammation. (asnjournals.org)
• C5a is a powerful chemoattractant for neutrophils, and ligation by C5a of C5aR/CD88 activates neutrophils. (asnjournals.org)
• Blockade of C5a or C5a receptor (C5aR/CD88) ameliorates anti-MPO NCGN in mice. (asnjournals.org)

Protein28

• C5a exerts its effect through a G-protein coupled receptor, CD88. (sigmaaldrich.com)
• Generation of multiple fluid-phase C3b:plasma protein complexes during complement activation: possible implications in C3 glomerulopathies. (rndsystems.com)
• C5a exerts a pro-inflammatory effect via the G-protein-coupled receptor C5a anaphylatoxin chemotactic receptor 1 (C5aR1, also known as CD88) that is expressed on cells of myeloid origin1,2. (ovid.com)
• However, choriocapillaris endothelial cells in organ culture responded to C5a by increasing ICAM-1 mRNA and protein. (arvojournals.org)
• Human C5a is a plasma protein with potent chemoattractant and pro-inflammatory properties, and its overexpression correlates with severity of inflammatory diseases. (aspetjournals.org)
• These results define a new pharmacophore for C5a antagonist development and advance our understanding of ligand recognition and receptor activation of this G protein-coupled receptor. (aspetjournals.org)
• Complement anaphylatoxin C5a neuroprotects through mitogen-activated protein kinase-dependent inhibition of caspase 3. (semanticscholar.org)
• Complement protein C1q modulates neurite outgrowth in vitro and spinal cord axon regeneration in vivo. (semanticscholar.org)
• Human Complement Component C5a (C5a) is also known as C5,and is a protein fragment released from complement component C5. (acrobiosystems.com)
• Human complement 5a (C5a) anaphylatoxin receptor (CD88) phosphorylation sites and their specific role in receptor phosphorylation and attenuation of G protein-mediated responses. (uniprot.org)
• Complement activity was evaluated by measuring changes in the terminal protein C5a in serum, and results suggest marine mammal complement is less sensitive to gas bubbles than human complement, but the response varies between species. (unlv.edu)
• Complement component 4 (C4), in humans, is a protein involved in the intricate complement system, originating from the human leukocyte antigen (HLA) system. (wikipedia.org)
• 10 nM) of C5a, the protein kinase C-mediated phosphorylation of Ser-334 was essentially blocked. (jpt.com)
• Complement protein C5a is recognized as an important component of the alternative complement pathway. (gyrosproteintechnologies.com)
• C5a, a small activation fragment of the complement C5 protein induced by either classical or alternative pathway, is a potent proinflammatory mediator ( 1 ). (aacrjournals.org)
• Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. (springer.com)
• CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for factor I, has decay accelerating activity and is able to bind preferentially to C3b at host surfaces. (wikipedia.org)
• The Recombinant Human Complement Component C5a Protein has been validated for the following applications: Bioactivity. (fishersci.co.uk)
• C5a receptor ( receptor 1 komplementne komponente 5a , C5AR1 , CD88 , klaster diferencijacije 88 ) je G protein spregnuti receptor za C5a . (wikipedia.org)
• Roles of the ribosomal protein S19 dimer and the C5a receptor in pathophysiological functions of phagocytic leukocytes. (wikipedia.org)
• Mitogen-activated protein kinase activation requires two signal inputs from the human anaphylatoxin C5a receptor. (wikipedia.org)
• 1994). "Stabilization of C5a receptor--G-protein interactions through ligand binding. (wikipedia.org)
• One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. (springer.com)
• Depletion of plasma complement in vivo by a protein of cobra venom: its effect on various immunologic reactions. (springer.com)
• Furthermore, the structure and functions of several complement proteins as well as the protein-protein interactions that underlie these functions are now being investigated with the aid of cross-disciplinary approaches ranging from mathematics and biophysics to comparative phylogenesis, in silico studies, mimetics and proteomics. (upenn.edu)
• Our current research efforts focus on the structural-functional aspects of protein-protein interactions and the rational design of small-size complement inhibitors. (upenn.edu)
• Chemotaxins C5a and fMLP induce release of calprotectin (leucocyte L1 protein) from polymorphonuclear cells in vitro. (thefreedictionary.com)
• The latter fragment is the critical first protein that combines with C6, C7, C8, and multiple C9 proteins to form the MAC, the terminal, pore-forming complement protein complex responsible for lysis of cells and pathogens. (aacrjournals.org)

Anaphylatoxins9

• Human complement component C5a (C5a) is an enzymatically generated glycoprotein that belongs to a family of structurally and functionally related proteins known as anaphylatoxins. (rndsystems.com)
• Complement activation leads to the production of the anaphylatoxins C3a and C5a, which are basic polypeptides of 74-77 aa derived from the α-chains of their parent proteins. (jimmunol.org)
• Identifying mechanisms through which complement anaphylatoxins modulate inflammation in the retina may provide a rationale for targeted drug design. (molvis.org)
• Activation of the complement cascade generates anaphylatoxins including C5a and C3a. (ovid.com)
• Along the way, 70- to 80-residue pro-inflammatory anaphylatoxins C3a, C4a, and C5a are also produced. (aspetjournals.org)
• Activation of the complement cascade results in the release of several anaphylatoxins, notable being C3a and C5a, leading to inflammation. (biomedcentral.com)
• When the complement system is activated, the generation of anaphylatoxins C3a and C5a can degranulate mast cells. (thefreedictionary.com)
• Subsequent steps of the complement cascade lead to formation of several effector molecules, including opsonization of pathogens, formation of the membrane attack complex inducing osmotic lysis of cells, and recruitment and activation of inflammatory cells by the anaphylatoxins complement C3a and C5a (25). (thefreedictionary.com)
• As a fundamental component of innate immunity, the complement cascade ( Fig. 1 ) contains some of the most powerful proinflammatory molecules in the body, including most notably the anaphylatoxins C3a and C5a. (aacrjournals.org)

Alternative pathway9

• The complement system has three independent pathways of complement activation: a classical pathway, an alternative pathway, a. (biomedcentral.com)
• Depending on the nature of complement activators, the classic pathway, the alternative pathway, or the more recently discovered lectin pathway is activated predominantly to produce C3 convertase. (medscape.com)
• Three pathways of complement activation: the classic pathway, lectin pathway, and alternative pathway, which of them converge at the level of complement component 3 (C3) convertase, from which functional products are generated in a sequential manner 5 . (nature.com)
• The alternative pathway of the complement system is an innate component of the immune system 's natural defense against infections. (wikipedia.org)
• The alternative pathway is one of three complement pathways that opsonize and kill pathogens. (wikipedia.org)
• The classical complement pathway typically requires antigen-antibody complexes for activation (specific immune response), whereas the alternative pathway can be activated by spontaneous C3 hydrolysis, foreign material, pathogens, or damaged cells. (wikipedia.org)
• Additionally, C3b generated by alternative pathway C3 convertase can attach to target surfaces and bind Bb, forming a C3 convertase that amplifies downstream complement proteins locally at the target surface. (aacrjournals.org)
• Recently, properdin, a positive regulator of the alternative pathway of complement, has been shown to bind to surfaces and promote complement activation. (pubmedcentralcanada.ca)
• Moreover, the mechanisms involved in alternative pathway-mediated complement activation or its consequences on infection in C. pneumoniae remain unknown. (pubmedcentralcanada.ca)

CD883

• The role of complement receptor C5a (CD88) was evaluated after cataract surgery in mice. (molvis.org)
• On binding to CD88, C5a evokes anaphylactic and chemotactic (attractant) responses, which mediate contraction of smooth muscles, enhance vascular permeability (VP), and promote leukocyte functions such as directed chemotaxis, degranulation, mediator release, and production of superoxide anions. (aacrjournals.org)
• Mycobacteria-primed macrophages and dendritic cells induce an up-regulation of complement C5a anaphylatoxin receptor (CD88) in CD3+ murine T cells. (qxmd.com)

Inflammatory24

• Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. (uniprot.org)
• Acute lung inflammatory injury in wild-type and C3-/- mice after deposition of IgG immune complexes was of equivalent intensity and was C5a dependent, but injury was greatly attenuated in Hc-/- mice (Hc encodes C5). (nih.gov)
• In addition, C5a augments inflammatory responses by triggering the production and release of proinflammatory cytokines, bioactive amines, superoxide anion, and intracellular enzymes from cells of myeloid origin. (jimmunol.org)
• The low levels of C5a and the absence of cytokines in milk from S. aureus-infected cows, compared to the high levels found in milk from E. coli-infected animals, mirror the differences in the severities of the two inflammatory reactions. (nih.gov)
• Complement system potent inflammatory cascade in wound infection, is important and altered wound healing. (scirp.org)
• Potent and selective C5a antagonists are predicted to be effective anti-inflammatory drugs, but no pharmacophore for small molecule antagonists has yet been developed, and it would significantly aid drug design. (aspetjournals.org)
• C5a is a potent chemotaxin for inflammatory cells and causes smooth muscle spasmogenesis as well as release of lysozomal enzymes, reactive oxygen species, and inflammatory cytokines (e.g. (aspetjournals.org)
• Sustained or aberrant complement activation is associated with tissue damage and inflammatory disease. (aspetjournals.org)
• The complement system is an essential effector of the humoral and cellular immunity involved in cytolysis and immune inflammatory responses. (biomedcentral.com)
• further we showed that mice genetically deficient of complement component C5 revealed a higher susceptibility to KA neurodegeneration [ 11 , 12 ] suggesting that in addition to their pro-inflammatory mechanisms, specific complement components may also mediate neuroprotection. (biomedcentral.com)
• We will investigate if the inflammatory complement factor C5a plays a role in epilepsy and if we can prevent development of seizures in mice. (edu.au)
• Accordingly, up-regulation of C5L2 may be of benefit in inflammatory states driven by C5a, including sepsis, asthma, cystic fibrosis, and chronic obstructive lung disease. (elsevier.com)
• The complement activation product, C5a, is an integral factor for regulation of inflammatory responses. (bio-zentrum.com)
• To research how wide the spectral range of C5a governed mediators is certainly, the concentrations of 23 inflammatory mediators had been examined with a multiplexing bead-based assay (Desk 1). (bio-zentrum.com)
• These results demonstrate that this strong proinflammatory anaphylatoxin C5a in high concentrations can mediate anti-inflammatory effects in primed macrophages, which may be beneficial to prevent excessive inflammation. (bio-zentrum.com)
• Complement activation exerts a wide range of effects that makes it ideal as both an effector mechanism and coordinator of immune/inflammatory responses. (frontiersin.org)
• As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. (springer.com)
• Remarkably, this list of inflammatory entities has a strong overlap with diseases that are regulated by complement suggesting a link between B-1 cells and the complement system. (frontiersin.org)
• Complement, a phylogenetically conserved arm of innate immunity, functions together with the adaptive immune response by serving as an important inflammatory mediator of antigen-antibody interactions. (upenn.edu)
• In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed. (hindawi.com)
• For example, the complement system participates in inflammatory reactions and facilitates removal of invading pathogens. (mddionline.com)
• The contribution of the complement cascade to acute inflammation is well established, as is the continuous activation and consumption of complement proteins in chronic inflammatory states ( 7 , 8 ). (aacrjournals.org)
• Since its discovery, the complement system has been primarily considered an effector of innate immunity with the ability to "complement" antibody-mediated clearance of foreign pathogens, dispose of dead cells, and cause inflammatory states ( 12 ). (aacrjournals.org)
• The complement anaphylatoxin C5a is a potent inflammatory mediator. (asnjournals.org)

MEMBRANE ATTACK7

• The ultimate product of complement activation is the membrane attack complex that is responsible for bacterial cell lysis. (aspetjournals.org)
• Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. (abcam.com)
• Which complement is part of the Membrane Attack Complex? (brainscape.com)
• The complement cascade can be activated by four different pathways, three of which converge at the level of the C3 component, leading to the cleavage of C3 and C5 to their activated forms, C3a and C5a, as well as the formation of the terminal membrane attack complex ( 17 , 18 ). (rupress.org)
• A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. (springer.com)
• The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and damaged material, inflammation to attract additional phagocytes, and activation of the cell-killing membrane attack complex . (wikipedia.org)
• IFX-1 completely blocks biological activity in and demonstrates high selectivity towards its target, C5a in human blood, thus leaving the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism. (thefreedictionary.com)

Fragment6

• C5a is a (11.2kDa) proteolytic fragment of the C5 α-chain through the action of C5 convertases in the classical and alternative complement pathway (C4b2a4b, C3bBb3b). (sigmaaldrich.com)
• Therefore, we studied, at several time points, the accumulation of neutrophils and the presence of the chemoattractant complement fragment C5a and of the cytokines interleukin-1beta (IL-1beta), tumor necrosis factor alpha, and IL-8 in milk after inoculation of E. coli or S. aureus in lactating bovine udders. (nih.gov)
• Using fluo-3 microfluorimetry, we have found that external application of the complement fragment C5a (4-10 nM) induced [Ca2+]i elevation in microglial cells in situ in corpus callosum slices. (mdc-berlin.de)
• The restoration of the extracellular Ca2+ concentration within 30-60 sec after the beginning of the complement fragment-induced [Ca2+]i elevation led to the recovery of the plateau phase. (mdc-berlin.de)
• Inhibition of the endoplasmic reticulum Ca2+ pumps with 500 nM thapsigargin transiently increased the [Ca2+]i and blocked the [Ca2+]i signals in response to subsequent complement fragment application. (mdc-berlin.de)
• A recent preprint study reported that lung biopsy samples from patients with severe COVID-19 showed widespread complement activation, characterized by C3a generation and C3-fragment deposition 6 . (nature.com)

Antibody10

• We offer Complement Component C5a Antibodies for use in common research applications: ELISA Capture (Matched Antibody Pair), ELISA Detection (Matched Antibody Pair), ELISA Standard (Matched Pair), Neutralization, Western Blot. (novusbio.com)
• Each Complement Component C5a Antibody is fully covered by our Guarantee+, to give you complete peace of mind and the support when you need it. (novusbio.com)
• Choose from our Complement Component C5a polyclonal antibodies and browse our Complement Component C5a monoclonal antibody catalog. (novusbio.com)
• In ELISAs, this antibody does not cross-react with recombinant human (rh) Complement Component C3a, rh alpha 2‑macroglobulin, recombinant mouse (rm) Complement Component C5a, or rmComplement Component C5d. (rndsystems.com)
• Complement C5 Monoclonal antibody specifically detects Complement C5 in Human,Baboon samples. (fishersci.com)
• 9. A chimeric antibody characterized in that it comprises at least one of the sequences corresponding to SEQ ID NO: 2, 4, 6, 8, or 12, wherein the antibody recognizes a region corresponding to sequence 727-744 (SEQ ID NO:15) of the C5 component of human complement or a region having at least 80% homology thereto. (google.com)
• Importantly, treatment of patients with an anti-C5a antibody led to immediate clinical improvement, as measured by increased lung oxygenation and decreased systemic inflammation 6 . (nature.com)
• This antibody recognises the C5a-R receptor but does not inhibit the binding of C5a to its receptor. (abcam.com)
• Tissue factor: A link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. (thefreedictionary.com)
• This antibody reacts with a neo-epitope on C5a that is formed upon cleavage of C5 into C5a and C5b. (genetex.com)

Proteins18

• Human C3a and C5a were produced after cleavage of their parent proteins, C3 and C5, respectively, using a fluid phase C3/C5 convertase, CVF, and Bb ( 28 ). (jimmunol.org)
• The complement system is part of the innate immune system and is composed of a diverse array of structural proteins and enzymes that promote or inhibit complement activation, which, in turn, leads to target cell chemotaxis, cellular activation, lysis, or apoptosis. (arvojournals.org)
• The complement pathway is comprised of many small proteins that become activated in order to clear pathogens from an organism. (scistart.co)
• More specifically, the two proteins, Ch and Rg, function together as a medium for interaction between the Ab-Ag complex and other complement components. (wikipedia.org)
• The apparent absence of coupling of C5L2 with G proteins suggests that this receptor may modulate the biological activity of C5a, perhaps by acting as a decoy receptor. (elsevier.com)
• Keywords: Cecal ligation and puncture, sepsis, macrophages, Akt, MEK1/2 Launch Proteolytic cleavage of supplement proteins pursuing activation from the traditional, choice, and lectin pathways can generate significant quantities of the anaphylatoxin, C5a [1]. (bio-zentrum.com)
• 1 microgram/ml) inhibited both C5a- and C3a-triggered [Ca2+]i responses, suggesting the involvement of PTX-sensitive G-proteins in the signal transduction chain. (mdc-berlin.de)
• The complement system is a complex set of self-assembling proteins that have been implicated in the pathophysiology of ARDS and sepsis. (snu.ac.kr)
• Because C5a-primed polymorphonuclear neutrophils (PMNs) induce hyperpermeability and phosphorylation of adherens junction proteins in endothelial cells ( 8 , 9 ) and in a similar manner C5aAP induces transient hypotension and neutropenia in rats ( 10 ), a hypothesis was put forth that C5aAP interactions with PMNs can initiate a series of events leading to the enhancement of VP. (aacrjournals.org)
• Membrane-bound complement regulatory proteins as biomarkers and potential therapeutic targets for SLE. (springer.com)
• We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. (springer.com)
• Human C3/CVF hybrid proteins represent a novel class of biologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis. (springer.com)
• Human C3/cobra venom factor hybrid proteins for therapeutic complement depletion: in vivo activity and fine mapping of important domains. (springer.com)
• Our laboratory, extending its research beyond the scope of traditional complement pathobiology, has embraced this global and combinatorial approach to biomedical research and has been actively engaged in defining the function of complement proteins in several biological contexts and pathophysiological states. (upenn.edu)
• The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver , and normally circulating as inactive precursors ( pro-proteins ). (wikipedia.org)
• Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes . (wikipedia.org)
• Thus, the recent finding that complement proteins C3, C4, and C5a may aid tumor growth through immunosuppression ( 11 ) is unexpected and suggests an insidious and previously unrecognized relationship between the complement system and cancer. (aacrjournals.org)
• This Competitive Intelligence report about Complement C5 Inhibitors 2017 - Biosuperiors & Biosimilars provides a competitor evaluation in the field of mainly recombinant antibodies, but also proteins, peptides, RNA and small molecules acting as inibitors of complement C5 or antagonists of the C5a receptor as of March 2017. (researchandmarkets.com)

ELISA6

• Your search returned 190 Complement C5a desArg ELISA ELISA Kit across 11 suppliers. (biocompare.com)
• The procedure method was followed according to manufacturer's instructions (Elabscience, USA) utilizing C5a ELISA kit for conducting the test. (scirp.org)
• Development of new standards for C5a ELISA assays. (scistart.co)
• Serum C5a was measured using the specific human C5a ELISA kit. (fujita-hu.ac.jp)
• 33 Complement Component 5a (C5a) ELISA Kits from 7 manufacturers are available on www.antibodies-online.com. (antibodies-online.com)
• The complement split products C3a, C4a and C5a were measured using ELISA. (snu.ac.kr)

Pathway19

• Generation of C5a in the absence of C3: a new complement activation pathway. (nih.gov)
• This linkage between the complement and coagulation pathways may represent a new pathway of complement activation. (nih.gov)
• The ability for doctors to predict C5a levels and therefore tailor their treatment would allow for personalized medicine that would take into account not only patient susceptibility to infection, but also tolerance to drugs targeting this pathway. (scistart.co)
• Here we investigate complement activation products and their role in nuclear factor (NF)-κB activation and gene expression of the NLRP3 inflammasome pathway. (cdc.gov)
• Binding of factor H to C3b increases its inactivation by factor I. Properdin stabilizes it, preventing its inactivation by factors H and I. The alternate pathway does not result in a truly nonspecific activation of complement because it requires specific types of compounds for activation. (medscape.com)
• Complement activation at C3 and C4 was involved in organ damage, especially renal, in AAV at the alternative complement pathway, factor B and properdin component colocalized with C3 complement in the endothelium of the blood vessels. (clinicaltrials.gov)
• Furthermore, the common complement pathway was activated as reflected by increased C5a levels. (clinicaltrials.gov)
• After the creation of C5 convertase (either as (C3b) 2 BbP or C4b2a3b from the classical pathway), the complement system follows the same path regardless of the means of activation (alternative, classical, or lectin). (wikipedia.org)
• However, C5 inhibition by these agents can be partial, allowing residual terminal pathway activity to skew efficacy in cases of excessive complement activation, which is often seen in infections. (nature.com)
• A recently described pathway results in the generation of C5a in the absence of C3 ( 19 ). (rupress.org)
• Classical Complement Pathway Component C1q: Purification of Human C1q, Isolation of C1q Collagen-Like and Globular Head Fragments and Production of Recombinant C1q-Derivatives. (springer.com)
• Three biochemical pathways activate the complement system: the classical complement pathway , the alternative complement pathway , and the lectin pathway . (wikipedia.org)
• C5 is involved in the activation of the lytic pathway within the complement system, which is an important factor in innate immunity. (genetex.com)
• MBL or ficolin activation of mannose-associated serine proteases (MASP) results in cleavage of C2 and C4 similar to the C1 complex, with subsequent production of C3 convertase and complement cascade activation resembling the classic pathway. (aacrjournals.org)
• In a manner that requires activation of the alternative complement pathway, passive transfer of antibodies to mouse MPO (anti-MPO) induces a mouse model of ANCA NCGN that closely mimics human disease. (asnjournals.org)
• 3 Alternative complement pathway activation is pivotal in the pathogenesis of anti-MPO NCGN in mice. (asnjournals.org)
• 4 - 6 The relevance of alternative complement pathway activation to human AAV is supported by immunohistochemical demonstration of alternative complement pathway components at sites of AAV 7 , 8 and by correlation of plasma alternative complement pathway activation fragments with AAV disease activity. (asnjournals.org)
• 5 , 6 ANCA-activated neutrophils activate the alternative complement pathway. (asnjournals.org)
• Human neutrophils activated by human ANCA release factors that activate the alternative complement pathway. (asnjournals.org)

Neutrophils8

• C5a stimulation of human neutrophils leads to STAT3 phosphorylation on Ser 727 . (sigmaaldrich.com)
• C3a and C5a are known for their stimulatory effect on leukocytes including chemotaxis of neutrophils, eosinophils, and monocytes ( 1 , 2 , 3 , 4 , 5 ). (jimmunol.org)
• C5L2 is an enigmatic serpentine receptor that is co-expressed with the C5a receptor on many cells including polymorphonuclear neutrophils. (elsevier.com)
• It is well established that activation of the complement cascade alters functional responses of neutrophils (PMN) in the course of systemic inflammation and contributes to the development of organ failure [ 15 , 23 ]. (hindawi.com)
• Hyperglycemic inhibition of complement-mediated opsonization resulted in decreased phagocytosis efficiency by euglycemic neutrophils, such that neutrophil function was not directly inhibited by excess glucose. (hindawi.com)
• These neutrophils migrate through the blood vessels, passing through interstitial tissue to the site of injury or infection via chemotaxis mediated by interleukin-8 (IL-8), C5a , fMLP, and leukotriene B4. (thefreedictionary.com)
• C5a also acts directly on neutrophils to increase their adherence to vessel walls, their migration toward sites of antigen deposition, and their ability to ingest particles. (slideserve.com)
• 4 , 6 , 12 In turn, C5a primes neutrophils and increase ANCA antigen expression. (asnjournals.org)

Inflammation12

• C5a is also a potent chemokine which stimulates the locomotion of polymorphonuclear leukocytes and directs their migration toward sites of inflammation. (uniprot.org)
• C5a, in addition to being a direct mediator of inflammation, can induce both IL-8 (interleukin-8) synthesis and high levels of IL-8 release from monocytes. (sigmaaldrich.com)
• C5a is playing a role as Chemoattractant of macrophage and neutrophil to the site of inflammation, also induces increase oxidative burst, phagocytosis and release of granule enzyme. (scirp.org)
• Immune responses to nitrogen gas bubbles, particularly activation of inflammation via the complement cascade, have been linked to the development of symptoms and damage associated with decompression sickness (DCS) in humans. (unlv.edu)
• This work evaluated the complement response, indicative of inflammation, to in vitro nitrogen bubble exposures in several marine mammal species to assess whether a less-responsive immune system serves a protective role against DCS-like injury in these animals. (unlv.edu)
• C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis). (abcam.com)
• Which complement is an anaphylatoxin (induces inflammation)? (brainscape.com)
• In an era that nurtures the integrated study of biological systems as the prevalent concept in contemporary scientific thinking, complement research is being revisited and our current knowledge of this innate immune system is enriched by findings that point to novel functions that do not strictly correlate with immunological defense and surveillance, immune modulation or inflammation. (upenn.edu)
• Complement C5a-Induced Changes in Neutrophil Morphology During Inflammation. (upenn.edu)
• This article is sought to provide insights into the pathogenesis of multiorgan failure associated with systemic inflammation with particular focus on the role of the complement system. (hindawi.com)
• The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's cell membrane . (wikipedia.org)
• Nevertheless, emerging literature examining the mechanistic relationship between inflammation and cancer ( 4 , 9 , 10 ) has almost completely omitted the role of the complement cascade. (aacrjournals.org)

Convertase5

• C5a is a 74 amino acid (aa) peptide that is created by the activity of C5a convertase on the C5 alpha-chain. (rndsystems.com)
• In the first phase, a series of specific interactions leads to formation of intrinsic complement proteinase, termed C3 convertase. (medscape.com)
• C3b acts as an opsonin and also combines with other components to form the C5 convertase that cleaves C5 into C5a and C5b. (frontiersin.org)
• C5-convertase cleaves C5 into C5a and C5b. (wikipedia.org)
• The formation of a C3 convertase can also be prevented when a plasma protease called complement factor I cleaves C3b into its inactive form, iC3b. (wikipedia.org)

Activation of the complement8

• Activation of the complement pathways. (medscape.com)
• The activation of the complement cascade is requisite for its involvement in immune responses. (frontiersin.org)
• The purpose of this study was to determine if activation of the complement system occurs in pregnant women with acute pyelonephritis. (snu.ac.kr)
• Moreover the present invention refers to the nucleotide sequences coding for such antibodies and to the therapeutic use of both polypeptide and nucleotide sequences, in particular for the therapy of diseases involving tissue damage deriving from uncontrolled activation of the complement system. (google.com)
• A growing body of evidence has implicated excessive activation of the complement system, especially formation of the potent proinflammatory anaphylatoxin C5a in mediating deleterious host responses to bacterial infections and contributing to the development of sepsis, adverse outcomes, and death ( 16 , 18 , 20 ). (rupress.org)
• The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. (hindawi.com)
• Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. (hindawi.com)
• Now, they may soon add a new risk factor to the list: activation of the complement system. (scienceblog.com)

Recombinant3

• Based on evidence suggesting that reduced expression of glutamate receptor subunit 2 (GluR2) may influence apoptosis in neurons, we studied the effect of human recombinant C5a on GluR2 expression in response to glutamate neurotoxicity. (biomedcentral.com)
• Simultaneous addition of recombinant mouse C5a (100 nM) to LPS-activated PEMs affected the creation of most mediators researched (Desk 1). (bio-zentrum.com)
• The present invention refers to recombinant antibodies of human origin specific for the C5 component of the activated complement and characterised by the ability to inhibit the conversion of the C5 alpha chain to C5a and C5b. (google.com)

Antagonists7

• Several small-molecule competitive antagonists for C5aR1, such as W-540115and NDT95137276, have been identified by C5a radioligand-binding assays4. (ovid.com)
• Here, to study the mechanism of action of C5a antagonists, we determine the structure of a thermostabilized C5aR1 (known as C5aR1 StaR) in complex with NDT9513727. (ovid.com)
• Potent Cyclic Antagonists of the Complement C5a Receptor on Human Polymorphonuclear Leukocytes. (aspetjournals.org)
• A comparison of solution structures for the C terminus of C5a, small acyclic peptide ligands, and cyclic antagonists supports the importance of a turn for receptor binding. (aspetjournals.org)
• Development of C5a receptor antagonists. (wiley.com)
• These fundamental new insights, summarized herein, provide the foundation for testing the efficacy of various complement antagonists to improve kidney transplant function and long-term graft survival. (jci.org)
• The report includes a compilation of currently active projects in research and development of inhibitors of complement C5 or antagonists of the C5a recepotr. (researchandmarkets.com)

Inhibition5

• Pharmacological inhibition of complement C5a-C5a1 receptor signalling ameliorates disease pathology in the hSOD1G93A mouse model of amyotrophic lateral sclerosis. (semanticscholar.org)
• Inhibition of the serine proteases of the complement system. (springer.com)
• The effects of selective complement- and CD14-inhibition on the E. coli-induced tissue factor mRNA up-regulation, monocyte tissue factor expression and tissue factor functional activity in human whole blood. (springer.com)
• So much so, that inhibition of C5a levels by immunologic inhibitors may have a therapeutic role in some forms of ANCA positive vasculitis. (clinicaltrials.gov)
• These results suggest that hyperglycemia inhibited humoral effector recruitment, anaphylatoxin generation, and complement-mediated opsonization of S. aureus , suggesting that hyperglycemic inhibition of complement effectors may contribute to the increased risk and severity of S. aureus infections in diabetic patients. (hindawi.com)

Peptide6

• In contrast, C5a protected terminally differentiated human neuroblastoma cells from toxicity mediated by the amyloid Aβ peptide. (jimmunol.org)
• Tumor responses to radioimmunotherapy combined with peptide agonists of human C5a anaphylatoxin such as GCGYSFKPMPLaR (C5aAP) are two- to four-fold better, depending on the dose of C5aAP, than responses to radioimmunotherapy alone. (aacrjournals.org)
• DCs cultured from C5-deficient (C5(-/-)) and -sufficient (C5(+/+)) mice were infected with BCG in the presence or absence of the C5a peptide. (qxmd.com)
• Thus, C5a, an innate peptide, appears to play an important role in the generation of acquired immune responses in mice by regulating the Th1 response through modulation of IL-12p70 secretion from DCs. (qxmd.com)
• Synthetic peptide corresponding to Human C5a-R aa 1-31 (N terminal). (abcam.com)
• Sulfation plays a critical role in the association of the receptor with C5a, but no significant role in the ability of the receptor to transduce a signal and mobilize calcium in response to a small peptide agonist. (abcam.com)

Cascade8

• Complement C5a human is an important terminal component of the complement cascade. (sigmaaldrich.com)
• The complement system functions as an interactive sequence, with one reaction leading to another in the form of a cascade. (medscape.com)
• On the basis of its concentration, C5a can either positively or negatively modulate the production by macrophages of IL-17 family members as well as IL-23 via the phosphatidylinositol 3-kinase/Akt signaling cascade. (frontiersin.org)
• Emerging evidence over the last decade unexpectedly identified the complement cascade as a common thread in this process. (jci.org)
• Emerging evidence over the past 15 years supports the concept that the complement cascade, traditionally considered a component of innate immunity, unexpectedly regulates kidney IR injury, T cell and humoral alloimmunity that underlie transplant rejection, and progressive kidney injury that results in late graft failure. (jci.org)
• Furthermore, potential therapeutic strategies targeting the complement cascade to prevent the development of MOF as well as possible future research directions are addressed. (hindawi.com)
• The complement cascade comprises the classic, alternative, and MBL pathways. (aacrjournals.org)
• It facilitates the final steps of the cascade by splitting C5 into C5a and C5b. (aacrjournals.org)

Inhibitors5

• The response to C5a was blocked by inhibitors of phosphatidylinositol-3-kinase, src kinase, and of the epidermal growth factor (EGF) receptor (EGFR) as well as by neutralizing Abs against the EGFR and heparin-binding EGF-like factor. (jimmunol.org)
• Inhibitors of the complement system have long been of interest as potential drugs for the treatment of diseases such as sepsis, rheumatoid arthritis, Crohn's disease and ischaemia-reperfusion injuries1. (ovid.com)
• The chapters in this book cover a wide range of topics related to the development of complement therapeutics, ranging from the molecular and functional description of complement targets to the presentation of novel inhibitors, improved treatment strategies as well as examples of disease models and clinical applications. (springer.com)
• CR2-Mediated Targeting of Complement Inhibitors: Bench-to-Bedside Using a Novel Strategy for Site-Specific Complement Modulation. (springer.com)
• Proximal complement inhibitors (which target C3 or its upstream activators) could be more effective, but these are still in clinical development, and none has yet been approved, although limited data from phase II clinical trials are available. (nature.com)

ENDOTHELIAL-CELLS6

• C5a, but not C3a, was chemotactic for human immortalized dermal microvascular endothelial cells. (jimmunol.org)
• The generation of C5a peptides may lead to activation of choriocapillaris endothelial cells in AMD. (arvojournals.org)
• The sequence leading to the increased VP appears to be initiated by the interaction of C5aAP with C5a receptor expressed on PMNs followed by binding to endothelial cells of blood vessels. (aacrjournals.org)
• IL-1, TNFα and C5a [1] cause the endothelial cells of blood vessels near the site of infection to express cellular adhesion molecules , including selectins . (wikipedia.org)
• 1994). "C5a-induced expression of P-selectin in endothelial cells." . (wikipedia.org)
• During this journey, from circulating cells to endothelial cells, C. pneumoniae encounters the innate immune system, in which the complement system may play a fundamental role in controlling Chlamydia infection. (pubmedcentralcanada.ca)

Vivo9

• Our results clearly show that an antagonist of C5a receptor delays proliferation and EMT significantly both in vivo and in vitro. (molvis.org)
• Our present study with C5a receptor knock out (C5aRKO) mice corroborates that the deficiency of C5a renders C5aRKO mouse more susceptible to apoptotic injury in vivo . (biomedcentral.com)
• Our results suggest that C5a protects against apoptotic pathways in neurons in vitro and in vivo through regulation of GluR2 receptor expression. (biomedcentral.com)
• Here we show that in mice bearing a targeted deletion of C5L2, the biological activity of C5a/C5a desArg is enhanced both in vivo and in vitro. (elsevier.com)
• Importantly, peritoneal in vivo administration of C5a increased CXCL13 production. (frontiersin.org)
• Identification of the major phosphorylation sites in human C5a anaphylatoxin receptor in vivo. (wikipedia.org)
• These attributes are complemented by sophisticated, clinically relevant in vitro and in vivo models of the trauma impact and resulting complications to gain deep insights into the mechanistic complexity and regeneration potential post trauma as well as to evaluate innovative cell- and molecular based therapies. (uni-ulm.de)
• In the long-term perspective, a valid functional immune monitoring of the individual danger response on the background of various co-morbidities and adapted immune- and cell-based therapies, for example by complement intervention and large-scale GMPgrade cellular ex vivo expansion, are anticipated. (uni-ulm.de)
• Here we report in vivo studies evaluating the extent to which a hyperglycemic environment alters complement-mediated control of S. aureus infection in a rat peritonitis model. (hindawi.com)

Chemoattractant1

• The C5a chemoattractant receptor mediates mucosal defence to infection. (wikipedia.org)

Macrophages6

• Results and Dialogue Differential legislation of mediator creation by C5a We've recently reported the fact that production of many cytokines (IL-17, IL-23, IL-27)is certainly BSI-201 suppressed by C5a when within civilizations of LPS-activated peritoneal elicited macrophages (PEMs)[5, 14, 15]. (bio-zentrum.com)
• C5a has been identified as a powerful modulator of Toll-like receptor-induced cytokine and chemokine production by macrophages. (frontiersin.org)
• C5a can also alter cytokine and chemokine production by macrophages and other cells. (frontiersin.org)
• Complement C5a (anaphylatoxin) secreted by mycobacteria-infected macrophages regulates IL-12p70 production. (qxmd.com)
• 5] Farrell BE, Daniele RP, Lauffenburger DA (1990) Quantitative relationships between single-cell and cell-population model parameters for chemosensory migration responses of alveolar macrophages to C5a. (ubc.ca)
• Such stimulation also induced marked local C5 production by PerC macrophages and C5a generation. (frontiersin.org)

System33

• The complement system has been shown to mediate renal ischemia-reperfusion (I/R) injury. (rug.nl)
• The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). (molvis.org)
• The complement system is a crucial component of the host response to infection and tissue damage. (ovid.com)
• The complement system plays a crucial role in the progression of age-related macular degeneration (AMD). (arvojournals.org)
• As a first step we have decided to analyze the effect of complement component 5 (C5) in this system. (molvis.org)
• The Complement System Component C5a Produces Thermal Hyperalgesia via Macrophage-to-Nociceptor Signaling That Requires NGF and TRPV1. (semanticscholar.org)
• The complement system is thought to be involved in the pathogenesis of numerous neurological diseases. (biomedcentral.com)
• Problem or Unmet Need: The complement system is an important part of the immune system and is responsible for the clearance of infectious agents, such as bacteria or fungi. (scistart.co)
• For example, the severity of a dysfunctional complement system can lead to fatal diseases and infections. (wikipedia.org)
• The complement system is a major effector of humoral immunity and natural immunity. (biomedcentral.com)
• Both the complement system and the interleukin (IL)-17 cytokine family protect against extracellular pathogens by enhancing innate immune functions. (frontiersin.org)
• The complement system provides an important first line of defense against extracellular pathogens such as bacteria and fungi. (frontiersin.org)
• The broad and up-to-date overview on a highly versatile and dynamic field renders this book an indispensable source of information for researchers and clinicians dealing with therapeutic and disease-related aspects of the human complement system. (springer.com)
• Paroxysmal nocturnal hemoglobinuria and the complement system: recent insights and novel anti-complement strategies. (springer.com)
• Complement system activation in cardiac and skeletal muscle pathology: Friend or foe? (springer.com)
• Recent reports suggest that complement system contributes to allograft rejection. (nature.com)
• Dysregulation of the complement system has been implicated in several diseases and pathologies. (wikipedia.org)
• Here, we urge immunologists and clinicians to consider the potential of targeting the complement system in these patients. (nature.com)
• The complement system is an essential component of the innate immune response to several infectious agents ( 16 ). (rupress.org)
• The complement system in B cell regulation. (springer.com)
• Using complement as a model system we apply ideas and methods embodied in engineering, computer science, physics, chemistry, and other fields to address today's challenges in biomedical research. (upenn.edu)
• The complement system has been long appreciated as a major effector arm of the innate immune response. (upenn.edu)
• As a central entity of innate immunity, the complement system is immediately activated after trauma or infection in order to control the replication of intruding pathogens. (hindawi.com)
• Previous studies strongly suggest a mutual crosstalk between the complement and the coagulation system [ 27 - 30 ]. (hindawi.com)
• Due to the complex nature of plasmatic cascades and their interconnections, the role and regulations of the complement system, especially in states of disease, are still inadequately understood. (hindawi.com)
• These in vitro results suggested that the complement system, a major contributor to innate immune host defenses against S. aureus [ 14 - 16 ], was significantly inhibited by hyperglycemic conditions in responding to S. aureus . (hindawi.com)
• It has been assumed that immunoglobulin G (IgG) antivenoms could activate the complement system through Fc and induce early adverse reactions (EARs). (ajtmh.org)
• 2 fragments can also activate the complement system. (ajtmh.org)
• The complement system can be recruited and brought into action by antibodies generated by the adaptive immune system . (wikipedia.org)
• Ehrlich introduced the term "complement" as part of his larger theory of the immune system. (wikipedia.org)
• Ehrlich, therefore, named this heat-labile component "complement," because it is something in the blood that "complements" the cells of the immune system. (wikipedia.org)
• The complement system is usually imp. (scienceblog.com)
• The complement system is a central component of the innate immune response and is involved in many functions, including recognition, opsonization, phagocytosis, and destruction of foreign cells, as well as generation of chemotactic fragments (C3a and C5a) and activation of adaptive immunity ( 30 , 32 , 51 ) Three pathways of complement activation are known: the classical, lectin, and alternative pathways. (pubmedcentralcanada.ca)

Mechanisms involved in C5a-mediated neuroprotection1

• In this study we explored the potential mechanisms involved in C5a-mediated neuroprotection. (semanticscholar.org)

Binds1

• [3] Complement factor H preferentially binds to vertebrate cells (because of affinity for sialic acid residues), allowing preferential protection of host (as opposed to bacterial) cells from complement-mediated damage. (wikipedia.org)

Inhibitor2

• Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates. (upenn.edu)
• NEW YORK--( BUSINESS WIRE )-- IVERIC bio, Inc. (Nasdaq: ISEE) today announced initial topline data confirming that Zimura® (avacincaptad pegol), the Company's complement factor C5 inhibitor, met its prespecified primary endpoint in reducing the rate of geographic atrophy (GA) growth in patients with dry age-related macular degeneration (AMD) in a randomized, controlled Phase 2b clinical trial. (businesswire.com)

Induce2

• Indeed, binding of C5adesArg or C5a to C5L2 will not induce rapid Ca2+ currents[9]. (bio-zentrum.com)
• Our data suggest that complement factors induce [Ca2+]i responses by Ca2+ release from internal pools and subsequent activation of Ca2+ entry controlled by the filling state of the intracellular Ca2+ depots. (mdc-berlin.de)

Antibodies2

• Our Complement Component C5a Antibodies can be used in a variety of model species: Mouse. (novusbio.com)
• In the early 20th century, this controversy was resolved when it became understood that complement can act in combination with specific antibodies, or on its own in a non-specific way. (wikipedia.org)

Sepsis3

• This finding may have clinical implications since blocking C5a improves ARDS in experimental sepsis. (snu.ac.kr)
• In humans, the plasma levels of complement activation products rise early, are persistently elevated in patients after thermal injury, trauma, and sepsis, and correlate with the severity of injury and inversely with the outcome [ 16 - 22 ]. (hindawi.com)
• In experimental sepsis, the blockade of complement anaphylatoxin C5a virtually prevented the appearance of MOF and improved the outcome [ 24 - 26 ]. (hindawi.com)

C5L21

• A second C5a receptor, C5L2 (GPR77), has been identified [8]. (bio-zentrum.com)

Neutrophil2

• These data provide evidence that C5a is crucially involved in the pathogenesis of renal I/R injury by modulation of neutrophil-dependent as well as neutrophil-independent pathways, which include the regulation of CXC chemokines but not TNF-alpha or apoptotic pathways. (rug.nl)
• Those resembling erythema nodosum (EN) show small vessel vasculitis and perivascular lymphocytic and mononuclear cell infiltration and fibrin deposition in the vessel wall, while the punched out ulcers are characterized by a leucocytoclastic vasculitis (neutrophil infiltrate) with fibrinoid necrosis. (angelfire.com)

Proinflammatory4

• Complement activation products and proinflammatory cytokines are associated with this polymorphism at the systemic level, but less is known of the associations in the outer retina of the genotyped eye. (cdc.gov)
• Whereas proinflammatory mediators had been suppressed by C5a, the exceptional acquiring was that just IL-10 and G-CSF had been amplified (by 103% and 197%, respectively). (bio-zentrum.com)
• In addition, many studies noticed strong increased plasma levels of the anaphlatoxin C5a that has a strong proinflammatory activity on the endothelium of vessels that may be related to disease severity. (clinicaltrials.gov)
• The proinflammatory mediators C3a and C5a are essential for liver regeneration. (thefreedictionary.com)

Mice5

• Injury in lungs of C3-/- mice and C5a levels in bronchoalveolar lavage (BAL) fluids from these mice were greatly reduced in the presence of antithrombin III (ATIII) or hirudin but were not reduced in similarly treated C3+/+ mice. (nih.gov)
• An antagonist specific to C5a receptor was administered intraperitoneally to mice. (molvis.org)
• In C5aRKO mice we found that the neurons are more susceptible to excitotoxicity resulting in apoptotic injury in the absence of the C5a receptor compared to WT control mice. (biomedcentral.com)
• Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3 −/− ) as skin graft donors or recipients. (nature.com)
• As IL-12p70 regulates Th1 immunity against mycobacteria in mice, we examined the effects of C5a on IL-12p70 secretion by murine DCs and Th1 immunity. (qxmd.com)

Pathogenesis1

• These data provide evidence implicating C5/ C5a in the pathogenesis of CM. (rupress.org)

Conditions such as Alzheimer's disease1

• More recently, a role of C5a in neurodegenerative conditions such as Alzheimer's disease has been identified3. (ovid.com)

Immune9

• Complement-mediated tissue injury in humans occurs upon deposition of immune complexes, such as in autoimmune diseases and acute respiratory distress syndrome. (nih.gov)
• Furthermore, immune precipitations showed that the EGFR was phosphorylated following stimulation with C5a. (jimmunol.org)
• The consequences of complement activation vary depending on the physiological context and timing during an immune (innate or adaptive) response. (frontiersin.org)
• however, complement components have the ability to substantially alter immune responses by modulating the local cytokine milieu. (frontiersin.org)
• In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. (springer.com)
• This body of literature, to be reviewed herein, suggests that complement components produced by the liver as well as by kidney cells and immune cells play crucial roles as pathogenic mediators of transplant rejection in animals and humans. (jci.org)
• We also study the viral molecular mimicry and immune evasion strategies, as well as the evolution of complement biology. (upenn.edu)
• 6 mM) dramatically inhibited S. aureus -initiated complement-mediated immune effectors. (hindawi.com)
• Immune phenotypes in the NOD background consist of defects in antigen presentation, T lymphocyte repertoire, NK cell function, macrophage cytokine production, wound healing, and C5 complement. (jax.org)

Responses1

• Variation in the Hemostatic Complement (C5a) Responses to in Vitro Nit" by Laura A. Thompson, Allyson G. Hindle et al. (unlv.edu)

Chemotactic receptor1

• The chemotactic receptor for human C5a anaphylatoxin. (wikipedia.org)

Vascular permeability1

• Localized injection of C5a increases vascular permeability. (jimmunol.org)

Fragments1

• Similarly, application of complement fragments C5a (0.1-10.0 nM) or C3a (100 nM) generates biphasic [Ca2+]i transients composed of an initial peak followed by a plateau in cultured microglia. (mdc-berlin.de)

Potent2

• Complement activation leads to the generation of many potent effectors including anaphylatoxin C5a. (scirp.org)
• Fueled by novel research insight and the marketing of the first complement-targeted drugs, a plethora of highly creative treatment approaches and potent drug candidates have recently emerged and are currently evaluated in disease models and clinical trials. (springer.com)

Elevated C5a levels1

• Early detection of «at risk" populations for elevated C5a levels. (scistart.co)

Regulates1

• Here, we demonstrate for the first time that C5a regulates B-1 cell steady-state dynamics within the peritoneum, the spleen, and the BM. (frontiersin.org)

Acute4

• It was found that the highest concentration of C5a was found at 120 hours after patients hospitalization who were with wound infection, and the mean value of C5a was 4898 pg/ml. 4661 pg/ml of C5a was recorded among patients with acute-phase infection compared to 4387 pg/ml concentration of the same complement among control group without wound infection at 96 hours post residence in hospital. (scirp.org)
• A complement 5a (C5a) revealed a very high concentration in acute-phase of wound infections. (scirp.org)
• METHODS: A cross-sectional study was conducted to determine the plasma concentrations of C3a, C4a and C5a (i.e., complement split products) in pregnant patients with acute pyelonephritis (n=38) and normal pregnant women (n=38). (snu.ac.kr)
• and 3) concentrations of C3a, C4a and C5a were not different among patients with acute pyelonephritis with and without bacteremia. (snu.ac.kr)

Serum7

• In serum, proteolytic processing removes the C-terminal arginine, creating a low activity C5a desArg74 molecule. (rndsystems.com)
• exhibits biological activities similar to serum-derived C5a. (sigmaaldrich.com)
• Organ cultures of human choroid were incubated in C5a or bovine serum albumin (BSA) followed by quantitative immunohistochemistry and quantitative PCR for ICAM-1. (arvojournals.org)
• This study aimed to determine whether donor gender affects levels of serum terminal complement component C5a and oxidative stress in pediatric living related liver transplantation (LRLTx) recipients. (fujita-hu.ac.jp)
• Results: C5a serum levels were higher in the 29 recipients who received their grafted livers from female donors than in the 14 recipients who received their grafted livers from male donors. (fujita-hu.ac.jp)
• Conclusions: Pediatric LRLTx patients who receive their grafts from female donors exhibit higher levels of serum C5a that probably plays a role in the immunological response against grafted livers from female donors in LTx. (fujita-hu.ac.jp)
• A prominent increase of serum C5a levels was also observed. (nature.com)

Mediator1

• TABLE 1 Regulation of macrophage-derived mediators by C5a C5a promotes release of G-CSF via Akt and MEK1/2 The current studies were focused on G-CSF, which was the mediator most potently enhanced by C5a in PEMs(Table 1). (bio-zentrum.com)

Tissue1

• In addition we study the involvement of various complement components with developmental pathways and the role of complement in tissue regeneration, early hematopoietic development and cancer. (upenn.edu)

Cytokine1

• The glial C5aRs are functionally competent since C5a stimulates calcium fluxes, induces cytokine transcription, triggers rearrangement of the cytoskeleton, and stimulates chemotactic activity of the cells ( 11 , 15 , 16 , 17 , 18 ). (jimmunol.org)

Pathogens1

• Activation of complement represents one means of natural resistance to infection from a wide variety of potential pathogens. (pubmedcentralcanada.ca)

Role6

• Indeed, it has been suggested that endothelial cell-derived superoxide generation played a role in C5a-mediated pulmonary injury ( 16 ). (jimmunol.org)
• The role of complement in tumor growth. (semanticscholar.org)
• Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful Cardiac Regeneration. (semanticscholar.org)
• The role of MASP-1/3 in complement activation. (springer.com)
• Interestingly, up to now, no data exist regarding the role of complement in B-1 cell biology. (frontiersin.org)
• An important caveat is that, although complement activation has been associated with the pathophysiology of ARDS caused by various underlying diseases 5 , clinical data on the role of complement activation in the development of SARS-CoV-2-associated ARDS are scarce. (nature.com)

DesArg1

• Clone C17/5 reacts with human C5a/C5a(desArg) and cross-reacts with baboon C5a/C5a(desArg). (fishersci.com)

Stimulation1

• Complement-activated (C5a) cellular antigen stimulation test. (webmd.com)