Complement Factor D
Ecchymosis
Complement Hemolytic Activity Assay
Complement Pathway, Alternative
Complement Factor H
Complement Factor B
Complement Factor I
Complement C3
Complement Activation
Complement System Proteins
Complement C3b
Complement Activating Enzymes
Complement C2
Complement C3b Inactivator Proteins
Complement C4
Complement C5
Macular Degeneration
Complement C3-C5 Convertases
Complement C5a
Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D. (1/132)
The crystal structure of profactor D, determined at 2.1 A resolution with an Rfree and an R-factor of 25.1 and 20.4%, respectively, displays highly flexible or disordered conformation for five regions: N-22, 71-76, 143-152, 187-193 and 215-223. A comparison with the structure of its mature serine protease, complement factor D, revealed major conformational changes in the similar regions. Comparisons with the zymogen-active enzyme pairs of chymotrypsinogen, trypsinogen and prethrombin-2 showed a similar distribution of the flexible regions. However, profactor D is the most flexible of the four, and its mature enzyme displays inactive, self-inhibited active site conformation. Examination of the surface properties of the N-terminus-binding pocket indicates that Ile16 may play the initial positioning role for the N-terminus, and Leu17 probably also helps in inducing the required conformational changes. This process, perhaps shared by most chymotrypsinogen-like zymogens, is followed by a factor D-unique step, the re-orientation of an external Arg218 to an internal position for salt-bridging with Asp189, leading to the generation of the self-inhibited factor D. (+info)Calcium-independent haemolysis via the lectin pathway of complement activation in the guinea-pig and other species*. (2/132)
We previously reported that complement-dependent haemolysis of sheep erythrocytes (E) coated with mannan (M) and sensitized with human mannan-binding lectin (MBL) via the lectin pathway in man occurs in Mg-EGTA and requires alternative pathway amplification. Calcium was required for MBL binding to E-M, but once the E-M-MBL intermediate was formed, MBL was retained and haemolysis occurred in the absence of calcium. Comparable or greater lectin pathway haemolysis in the absence of calcium was observed upon incubation of E-M-MBL in guinea-pig, rat, dog and pig sera, and was further investigated in the guinea-pig, in which titres were much higher ( approximately 14-fold) than in man, and in contrast to humans, greater than classical pathway haemolytic activity. As in human serum, no lysis was observed in C4- or C2-deficient guinea-pig serum until purified C4 or C2, respectively, were restored. However, lectin pathway haemolytic activity in the guinea-pig did not require the alternative pathway. Removal (>98%) of factor D activity by three sequential passages through Sephadex G-75, resulting in serum which retained a normal classical pathway but no alternative pathway haemolytic activity, did not reduce the ability of guinea-pig serum to mediate haemolysis via the lectin pathway. Further, the C3-convertase formed via the lectin pathway (E-M-MBL-C4,2) lysed in C2-deficient guinea-pig but not human serum chelated with EDTA, a condition which precludes alternative pathway amplification. Thus, lectin pathway haemolysis occurs efficiently in guinea-pig serum, in the absence of calcium and without requirement for alternative pathway amplification. The guinea-pig provides a model for studying the assembly and haemolytic function of a lectin pathway which contrasts with the lectin pathway of man, and allows for comparisons that may help clarify the role of this pathway in complement biology. (+info)The Arthus reaction in rodents: species-specific requirement of complement. (3/132)
We induced reverse passive Arthus (RPA) reactions in the skin of rodents and found that the contribution of complement to immune complex-mediated inflammation is species specific. Complement was found to be necessary in rats and guinea pigs but not in C57BL/6J mice. In rats, within 4 h after initiation of an RPA reaction, serum alternative pathway hemolytic titers decreased significantly below basal levels, whereas classical pathway titers were unchanged. Thus the dermal reaction proceeds coincident with systemic activation of complement. The serine protease inhibitor BCX 1470, which blocks the esterolytic and hemolytic activities of the complement enzymes Cls and factor D in vitro, also blocked development of RPA-induced edema in the rat. These data support the proposal that complement-mediated processes are of major importance in the Arthus reaction in rats and guinea pigs, and suggest that BCX 1470 will be useful as an anti-inflammatory agent in diseases where complement activation is known to be detrimental. (+info)Mutational analysis of the primary substrate specificity pocket of complement factor B. Asp(226) is a major structural determinant for p(1)-Arg binding. (4/132)
Factor B is a serine protease, which despite its trypsin-like specificity has Asn instead of the typical Asp at the bottom of the S(1) pocket (position 189, chymotrypsinogen numbering). Asp residues are present at positions 187 and 226 and either one could conceivably provide the negative charge for binding the P(1)-Arg of the substrate. Determination of the crystal structure of the factor B serine protease domain has revealed that the side chain of Asp(226) is within the S(1) pocket, whereas Asp(187) is located outside the pocket. To investigate the possible role of these atypical structural features in substrate binding and catalysis, we constructed a panel of mutants of these residues. Replacement of Asp(187) caused moderate (50-60%) decrease in hemolytic activity, compared with wild type factor B, whereas replacement of Asn(189) resulted in more profound reductions (71-95%). Substitutions at these two positions did not significantly affect assembly of the alternative pathway C3 convertase. In contrast, elimination of the negative charge from Asp(226) completely abrogated hemolytic activity and also affected formation of the C3 convertase. Kinetic analyses of the hydrolysis of a P(1)-Arg containing thioester by selected mutants confirmed that residue Asp(226) is a primary structural determinant for P(1)-Arg binding and catalysis. (+info)C/EBPbeta, when expressed from the C/ebpalpha gene locus, can functionally replace C/EBPalpha in liver but not in adipose tissue. (5/132)
Knockout of C/EBPalpha causes a severe loss of liver function and, subsequently, neonatal lethality in mice. By using a gene replacement approach, we generated a new C/EBPalpha-null mouse strain in which C/EBPbeta, in addition to its own expression, substituted for C/EBPalpha expression in tissues. The homozygous mutant mice C/ebpalpha(beta/beta) are viable and fertile and show none of the overt liver abnormalities found in the previous C/EBPalpha-null mouse line. Levels of hepatic PEPCK mRNA are not different between C/ebpalpha(beta/beta) and wild-type mice. However, despite their normal growth rate, C/ebpalpha(beta/beta) mice have markedly reduced fat storage in their white adipose tissue (WAT). Expression of two adipocyte-specific factors, adipsin and leptin, is significantly reduced in the WAT of C/ebpalpha(beta/beta) mice. In addition, expression of the non-adipocyte-specific genes for transferrin and cysteine dioxygenase is reduced in WAT but not in liver. Our study demonstrates that when expressed from the C/ebpalpha gene locus, C/EBPbeta can act for C/EBPalpha to maintain liver functions during development. Moreover, our studies with the C/ebpalpha(beta/beta) mice provide new insights into the nonredundant functions of C/EBPalpha and C/EBPbeta on gene regulation in WAT. (+info)Induction of adipocyte-specific gene expression is correlated with mammary tumor regression by the retinoid X receptor-ligand LGD1069 (targretin). (6/132)
Targretin (LGD1069; a high-affinity ligand for the retinoid X receptors) is an efficacious chemotherapeutic and chemopreventive agent in the N-nitroso-N-methylurea-induced rat mammary carcinoma model. To evaluate the molecular action of LGD1069 in mammary carcinoma we have examined gene expression patterns in controls and nonresponding tumors compared with tumors undergoing regression (responding) by LGD1069. When compared with controls or nonresponding tumors, the expression of adipocyte-related genes such as adipocyte P2 (aP2), adipsin, peroxisome proliferator-activated receptor gamma (PPARgamma), and lipoprotein lipase was elevated in LGD1069-responding tumors. Further analysis showed that gene expression changes occurred rapidly, in as little as 6 h, after the first dose of LGD1069. Immunohistochemical analysis showed that aP2 protein was also highly expressed in responding tumors when compared with control or nonresponding tumors. More importantly, aP2 protein was localized in the tumor cells in addition to the adipocytes present in the tumors. Similar changes in gene expression and inhibition in growth were seen in tumor cells (cloned from N-nitroso-N-methylurea-induced carcinoma) exposed to LGD1069 in vitro. These data suggest that tumor regression by LGD1069 involves differentiation induction along the adipocyte lineage. (+info)A comparison of on-line hemodiafiltration and high-flux hemodialysis: a prospective clinical study. (7/132)
Some of the morbidity associated with chronic hemodialysis is thought to result from retention of large molecular weight solutes that are poorly removed by diffusion in conventional hemodialysis. Hemodiafiltration combines convective and diffusive solute removal in a single therapy. The hypothesis that hemodiafiltration provides better solute removal than high-flux hemodialysis was tested in a prospective, randomized clinical trial. Patients were randomized to either on-line postdilution hemodiafiltration or high-flux hemodialysis. The groups did not differ in body size, treatment time, blood flow rate, or net fluid removal. The filtration volume in hemodiafiltration was 21 +/-1 L. Therapy prescriptions were unchanged for a 12-mo study period. Removal of both small (urea and creatinine) and large (ss(2)-microglobulin and complement factor D) solutes was significantly greater for hemodiafiltration than for high-flux hemodialysis. The increased urea and creatinine removal did not result in lower pretreatment serum concentrations in the hemodiafiltration group. Pretreatment plasma beta(2)-microglobulin concentrations decreased with time (P< 0.001); however, the decrease was similar for both therapies (P = 0.317). Pretreatment plasma complement factor D concentrations also decreased with time (P<0.001), and the decrease was significantly greater with hemodiafiltration than with high-flux hemodialysis (P = 0.010). The conclusion is that on-line hemodiafiltration provides superior solute removal to high-flux hemodialysis over a wide molecular weight range. The improved removal may not result in lower pretreatment plasma concentrations, however, possibly because of limitations in mass transfer rates within the body. (+info)A family with complement factor D deficiency. (8/132)
A complement factor D deficiency was found in a young woman who had experienced a serious Neisseria meningitidis infection, in a deceased family member with a history of meningitis, and in three relatives without a history of serious infections. The patient and these three relatives showed a normal activity of the classical complement pathway, but a very low activity of the alternative complement pathway and a very low capacity to opsonize Escherichia coli and N. meningitidis (isolated from the patient) for phagocytosis by normal human neutrophils. The alternative pathway-dependent hemolytic activity and the opsonizing capacity of these sera were restored by addition of purified factor D. The family had a high degree of consanguinity, and several other family members exhibited decreased levels of factor D. The gene encoding factor D was found to contain a point mutation that changed the TCG codon for serine 42 into a TAG stop codon. This mutation was found in both alleles of the five completely factor D-deficient family members and in one allele of 21 other members of the same family who had decreased or low-normal factor D levels in their serum. The gene sequence of the signal peptide of human factor D was also identified. Our report is the first, to our knowledge, to document a Factor D gene mutation. The mode of inheritance of factor D deficiency is autosomal recessive, in accordance with the localization of the Factor D gene on chromosome 19. Increased susceptibility for infections in individuals with a partial factor D deficiency is unlikely. (+info)Complement Factor D is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Specifically, Factor D is a serine protease that is involved in the alternative pathway of the complement system.
In this pathway, Factor D helps to cleave another protein called Factor B, which then activates a complex called the C3 convertase. The C3 convertase cleaves complement component 3 (C3) into C3a and C3b, leading to the formation of the membrane attack complex (MAC), which creates a pore in the membrane of the target cell, causing its lysis and removal from the body.
Deficiencies or mutations in Complement Factor D can lead to an impaired alternative pathway and increased susceptibility to certain infections, particularly those caused by Neisseria bacteria. Additionally, abnormal regulation of the complement system has been implicated in a variety of diseases, including autoimmune disorders, inflammatory conditions, and neurodegenerative diseases.
Ecchymosis is a medical term that refers to a discoloration of the skin caused by the leakage of blood from ruptured blood vessels into the tissues beneath. It is typically caused by trauma or injury to the affected area, which results in the escape of blood from the damaged blood vessels. The escaped blood collects under the skin, causing a bruise or a purple, blue, or blackish patch on the skin's surface.
Ecchymosis can occur anywhere on the body and can vary in size and shape depending on the extent of the injury. While ecchymosis is generally harmless and resolves on its own within a few days to a week, it can be a sign of an underlying medical condition, such as a bleeding disorder or a blood vessel abnormality. In these cases, further evaluation and treatment may be necessary.
A Complement Hemolytic Activity Assay is a laboratory test used to measure the functionality and activity level of the complement system, which is a part of the immune system. The complement system is a group of proteins that work together to help eliminate pathogens from the body.
The assay measures the ability of the complement system to lyse (break open) red blood cells. This is done by mixing the patient's serum (the liquid portion of the blood) with antibody-coated red blood cells and incubating them together. The complement proteins in the serum will then bind to the antibodies on the red blood cells and cause them to lyse.
The degree of hemolysis (red blood cell lysis) is directly proportional to the activity level of the complement system. By measuring the amount of hemolysis, the assay can determine whether the complement system is functioning properly and at what level of activity.
This test is often used to diagnose or monitor complement-mediated diseases such as autoimmune disorders, infections, and some types of cancer. It may also be used to evaluate the effectiveness of treatments that target the complement system.
The alternative complement pathway is one of the three initiating pathways of the complement system, which is a part of the innate immune system that helps to clear pathogens and damaged cells from the body. The other two pathways are the classical and lectin pathways.
The alternative pathway is continuously activated at a low level, even in the absence of infection or injury, through the spontaneous cleavage of complement component C3 into C3a and C3b by the protease factor D in the presence of magnesium ions. The generated C3b can then bind covalently to nearby surfaces, including pathogens and host cells.
On self-surfaces, regulatory proteins like decay-accelerating factor (DAF) or complement receptor 1 (CR1) help to prevent the formation of the alternative pathway convertase and thus further activation of the complement system. However, on foreign surfaces, the C3b can recruit more complement components, forming a complex called the alternative pathway convertase (C3bBb), which cleaves additional C3 molecules into C3a and C3b.
The generated C3b can then bind to the surface and participate in the formation of the membrane attack complex (MAC), leading to the lysis of the target cell. The alternative pathway plays a crucial role in the defense against gram-negative bacteria, fungi, and parasites, as well as in the clearance of immune complexes and apoptotic cells. Dysregulation of the alternative complement pathway has been implicated in several diseases, including autoimmune disorders and atypical hemolytic uremic syndrome (aHUS).
Complement Factor H is a protein involved in the regulation of the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Specifically, Complement Factor H helps to regulate the activation and deactivation of the complement component C3b, preventing excessive or unwanted activation of the complement system and protecting host tissues from damage.
Complement Factor H is a crucial protein in maintaining the balance between the protective effects of the complement system and the potential for harm to the body's own cells and tissues. Deficiencies or mutations in Complement Factor H have been associated with several diseases, including age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and C3 glomerulopathy.
Complement Factor B is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. Specifically, Factor B is a component of the alternative pathway of the complement system, which provides a rapid and amplified response to microbial surfaces.
Factor B is cleaved by another protease called Factor D into two fragments, Ba and Bb. The formation of the C3 convertase (C3bBb) is essential for the activation of the alternative pathway. This complex can cleave and activate more C3 molecules, leading to a cascade of reactions that result in the formation of the membrane attack complex (MAC), which forms pores in the membranes of target cells, causing their lysis and elimination.
Deficiencies or mutations in Complement Factor B can lead to various complement-mediated diseases, such as atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD).
Complement Factor I is a protein involved in the regulation of the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Specifically, Complement Factor I is a serine protease that regulates the complement component C3b by cleaving it into inactive fragments, thereby preventing the excessive activation of the complement system and protecting host tissues from damage.
Complement Factor I functions in conjunction with other regulatory proteins, such as complement receptor 1 (CR1) and membrane cofactor protein (MCP), to control the activity of the complement system at various stages. Deficiencies or mutations in Complement Factor I have been associated with several diseases, including atypical hemolytic uremic syndrome (aHUS), age-related macular degeneration (AMD), and systemic lupus erythematosus (SLE).
Complement C3 is a protein that plays a central role in the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Complement C3 can be activated through three different pathways: the classical pathway, the lectin pathway, and the alternative pathway. Once activated, it breaks down into two fragments, C3a and C3b.
C3a is an anaphylatoxin that helps to recruit immune cells to the site of infection or injury, while C3b plays a role in opsonization, which is the process of coating pathogens or damaged cells with proteins to make them more recognizable to the immune system. Additionally, C3b can also activate the membrane attack complex (MAC), which forms a pore in the membrane of target cells leading to their lysis or destruction.
In summary, Complement C3 is an important protein in the complement system that helps to identify and eliminate pathogens and damaged cells from the body through various mechanisms.
Complement activation is the process by which the complement system, a part of the immune system, is activated to help eliminate pathogens and damaged cells from the body. The complement system consists of a group of proteins that work together to recognize and destroy foreign substances.
Activation of the complement system can occur through three different pathways: the classical pathway, the lectin pathway, and the alternative pathway. Each pathway involves a series of proteolytic reactions that ultimately result in the formation of the membrane attack complex (MAC), which creates a pore in the membrane of the target cell, leading to its lysis and removal.
The classical pathway is typically activated by the binding of antibodies to antigens on the surface of a pathogen or damaged cell. The lectin pathway is activated by the recognition of specific carbohydrate structures on the surface of microorganisms. The alternative pathway can be spontaneously activated and serves as an amplification loop for both the classical and lectin pathways.
Complement activation plays a crucial role in the immune response, but uncontrolled or excessive activation can also lead to tissue damage and inflammation. Dysregulation of complement activation has been implicated in various diseases, including autoimmune disorders, inflammatory conditions, and neurodegenerative diseases.
The complement system is a group of proteins found in the blood and on the surface of cells that when activated, work together to help eliminate pathogens such as bacteria, viruses, and fungi from the body. The proteins are normally inactive in the bloodstream. When they encounter an invading microorganism or foreign substance, a series of reactions take place leading to the activation of the complement system. Activation results in the production of effector molecules that can punch holes in the cell membranes of pathogens, recruit and activate immune cells, and help remove debris and dead cells from the body.
There are three main pathways that can lead to complement activation: the classical pathway, the lectin pathway, and the alternative pathway. Each pathway involves a series of proteins that work together in a cascade-like manner to amplify the response and generate effector molecules. The three main effector molecules produced by the complement system are C3b, C4b, and C5b. These molecules can bind to the surface of pathogens, marking them for destruction by other immune cells.
Complement proteins also play a role in the regulation of the immune response. They help to prevent excessive activation of the complement system, which could damage host tissues. Dysregulation of the complement system has been implicated in a number of diseases, including autoimmune disorders and inflammatory conditions.
In summary, Complement System Proteins are a group of proteins that play a crucial role in the immune response by helping to eliminate pathogens and regulate the immune response. They can be activated through three different pathways, leading to the production of effector molecules that mark pathogens for destruction. Dysregulation of the complement system has been linked to various diseases.
Complement C3b is a protein fragment that plays a crucial role in the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. C3b is generated during the activation of the complement system, particularly via the classical, lectin, and alternative pathways.
Once formed, C3b can bind covalently to the surface of microbes or other target particles, marking them for destruction by other components of the immune system. Additionally, C3b can interact with other proteins in the complement system to generate the membrane attack complex (MAC), which forms pores in the membranes of targeted cells, leading to their lysis and removal.
In summary, Complement C3b is a vital protein fragment involved in the recognition, tagging, and elimination of pathogens and damaged cells during the immune response.
Complement activating enzymes are proteins that play a crucial role in the activation of the complement system, which is a part of the immune system. The complement system is a complex series of biochemical reactions that help to eliminate pathogens and damaged cells from the body.
There are several types of complement activating enzymes, including:
1. Classical pathway activators: These include the C1, C4, and C2 components of the complement system. When activated, they trigger a series of reactions that lead to the formation of the membrane attack complex (MAC), which creates a pore in the membrane of the target cell, leading to its lysis.
2. Alternative pathway activators: These include factors B, D, and P. They are constantly active at low levels and can be activated by surfaces that are not normally found in the body, such as bacterial cell walls. Once activated, they also trigger the formation of the MAC.
3. Lectin pathway activators: These include mannose-binding lectin (MBL) and ficolins. They bind to carbohydrates on the surface of microbes and activate the complement system through the MBL-associated serine proteases (MASPs).
Overall, complement activating enzymes play a critical role in the immune response by helping to identify and eliminate pathogens and damaged cells from the body.
Complement C2 is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. Specifically, C2 is a component of the classical complement pathway, which is activated by the binding of antibodies to antigens on the surface of foreign particles or cells.
When the classical pathway is activated, C2 is cleaved into two fragments: C2a and C2b. C2a then binds to C4b to form the C3 convertase (C4b2a), which cleaves C3 into C3a and C3b. C3b can then go on to form the membrane attack complex, which creates a pore in the membrane of the target cell, leading to its lysis.
In summary, Complement C2 is a protein that helps to activate the complement system and destroy foreign particles or cells through the formation of the C3 convertase and the membrane attack complex.
Complement C3b inactivator proteins, also known as complement regulators or decay-accelerating factor (DAF), are a group of proteins that play a crucial role in regulating the complement system. The complement system is a part of the immune system that helps to eliminate pathogens and damaged cells from the body.
The complement C3b inactivator proteins include two main types: complement receptor 1 (CR1) and decay-accelerating factor (DAF). These proteins work by regulating the formation of the membrane attack complex (MAC), a protein structure that forms pores in the cell membrane, leading to cell lysis.
Complement C3b inactivator proteins bind to C3b and C4b components of the complement system, preventing them from forming the MAC. By doing so, they help to prevent excessive activation of the complement system, which can damage healthy cells and tissues.
Deficiencies or dysfunction of complement C3b inactivator proteins have been associated with several diseases, including autoimmune disorders, inflammatory diseases, and infectious diseases. Therefore, understanding the role of these proteins in regulating the complement system is essential for developing new therapies to treat these conditions.
Complement C4 is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Complement C4 is involved in the early stages of the complement activation cascade, where it helps to identify and tag foreign or abnormal cells for destruction by other components of the immune system.
Specifically, Complement C4 can be cleaved into two smaller proteins, C4a and C4b, during the complement activation process. C4b then binds to the surface of the target cell and helps to initiate the formation of the membrane attack complex (MAC), which creates a pore in the cell membrane and leads to lysis or destruction of the target cell.
Deficiencies or mutations in the Complement C4 gene can lead to various immune disorders, including certain forms of autoimmune diseases and susceptibility to certain infections.
Complement C5 is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. The complement system is a complex series of biochemical reactions that help to identify and destroy foreign substances, such as bacteria and viruses.
Complement C5 is one of several proteins in the complement system that are activated in a cascading manner in response to an activating event, such as the binding of an antibody to a pathogen. Once activated, Complement C5 can be cleaved into two smaller proteins, C5a and C5b.
C5a is a powerful anaphylatoxin, which means it can cause the release of histamine from mast cells and basophils, leading to inflammation and increased vascular permeability. It also acts as a chemoattractant, drawing immune cells to the site of infection or injury.
C5b, on the other hand, plays a role in the formation of the membrane attack complex (MAC), which is a protein structure that can punch holes in the membranes of pathogens, leading to their lysis and destruction.
Overall, Complement C5 is an important component of the immune system's response to infection and injury, helping to eliminate pathogens and damaged cells from the body.
Macular degeneration, also known as age-related macular degeneration (AMD), is a medical condition that affects the central part of the retina, called the macula. The macula is responsible for sharp, detailed vision, which is necessary for activities such as reading, driving, and recognizing faces.
In AMD, there is a breakdown or deterioration of the macula, leading to gradual loss of central vision. There are two main types of AMD: dry (atrophic) and wet (exudative). Dry AMD is more common and progresses more slowly, while wet AMD is less common but can cause rapid and severe vision loss if left untreated.
The exact causes of AMD are not fully understood, but risk factors include age, smoking, family history, high blood pressure, obesity, and exposure to sunlight. While there is no cure for AMD, treatments such as vitamin supplements, laser therapy, and medication injections can help slow its progression and reduce the risk of vision loss.
Complement C3-C5 convertases are proteins that play a crucial role in the activation of the complement system, which is a part of the immune system. The complement system helps to eliminate pathogens and damaged cells from the body by marking them for destruction and attracting immune cells to the site of infection or injury.
The C3-C5 convertases are formed during the activation of the complement component 3 (C3) protein, which is a central player in the complement system. The formation of the C3-C5 convertase involves two main steps:
1. C3 convertase formation: In this step, a complex of proteins called the C3 convertase is formed by the cleavage of C3 into C3a and C3b fragments. This complex can then cleave additional C3 molecules into C3a and C3b fragments, amplifying the complement response.
2. C5 convertase formation: In this step, the C3b fragment from the C3 convertase binds to another protein called C4b2a, forming a new complex called the C5 convertase. The C5 convertase can then cleave the C5 protein into C5a and C5b fragments.
The C5b fragment goes on to form the membrane attack complex (MAC), which creates a pore in the membrane of the target cell, leading to its lysis or destruction. The C3a and C5a fragments are small proteins called anaphylatoxins that can cause inflammation and attract immune cells to the site of infection or injury.
Overall, the formation of Complement C3-C5 convertases is a critical step in the activation of the complement system and plays a key role in the body's defense against pathogens and damaged cells.
Complement C5a is a protein fragment that is generated during the activation of the complement system, which is a part of the immune system. The complement system helps to eliminate pathogens and damaged cells from the body by tagging them for destruction and attracting immune cells to the site of infection or injury.
C5a is formed when the fifth component of the complement system (C5) is cleaved into two smaller fragments, C5a and C5b, during the complement activation cascade. C5a is a potent pro-inflammatory mediator that can attract and activate various immune cells, such as neutrophils, monocytes, and eosinophils, to the site of infection or injury. It can also increase vascular permeability, promote the release of histamine, and induce the production of reactive oxygen species, all of which contribute to the inflammatory response.
However, excessive or uncontrolled activation of the complement system and generation of C5a can lead to tissue damage and inflammation, contributing to the pathogenesis of various diseases, such as sepsis, acute respiratory distress syndrome (ARDS), and autoimmune disorders. Therefore, targeting C5a or its receptors has been explored as a potential therapeutic strategy for these conditions.
Complement factor I
Complement factor B
C3a (complement)
Complement component 3
Complement component 4B
Complement control protein
List of OMIM disorder codes
Complement (group theory)
Properdin deficiency
CFHR5
CFHR4
CFHR2
Nucleolin
IC3b
Genome-wide association study
Complement component 2
Total complement activity
Synovial fluid
James Markusen
Single-nucleotide polymorphism
L-selectin
Iptacopan
Personalized medicine
BioCryst Pharmaceuticals
Tuxedo Computers
Phagoptosis
CD59
Atypical hemolytic uremic syndrome
ARF5
CFHR3
Complement factor I - Wikipedia
Rattus norvegicus complement factor H (Cfh), mRNA - Nucleotide - NCBI
Complement factor H variant increases the risk of age-related macular degeneration
Multifactor Effects and Evidence of Potential Interaction between Complement Factor H Y402H and LOC387715 A69S in Age-Related...
Human Complement factor I CFI ELISA Kit - Gentaur.com
Complement factor H | BioVendor R&D
Factor D Inhibition Blocks Complement Activation Induced by Mutant Factor B Associated With Atypical Hemolytic Uremic Syndrome...
Complement C4 Deficiency - A Plausible Risk Factor for Non-Tuberculous Mycobacteria (NTM) Infection in Apparently...
Insights from Reliability-Based Design to Complement Load and Resistance Factor Design Approach - New Zealand Geotechnical...
Functional anatomy of complement Factor H - Fingerprint - University of Edinburgh Research Explorer
Complement Factor H: Function and Dysfunction | Abstract
Factor H preserves alternative complement function during ARDS linked to improved survival | European Respiratory Society
Complement Factor H Deficiency - FindZebra
Complement-Related Disorders: Background, Pathophysiology, Activation
CFIbase: Complement factor I deficiency | Liability
Complement factor I gene mutation and aseptic meningitis
Anti-Complement Factor D [I8/1] | Absolute Antibody
Complement C3 nephritic factor - North West London Pathology
Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration. - Nuffield Department of...
Preeclampsia, Hypoxia, Thrombosis, and Inflammation
How endothelial cells protect themselves from complement by expressing decay-accelerating factor (DAF) | Arthritis Research &...
Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: inhibition of late apoptosis and...
Endothelial function in pigs transgenic for human complement regulating factor<...
Complement factor H in AMD: Bridging genetic associations and pathobiology<...
RCSB PDB - 5O32: The structure of complement complex
Anti Human Complement Factor H Antibody, clone 028B-244.2.10X (10-10) | Bio-Rad
Control of adipose tissue cellularity by the terminal complement cascade | Nature Reviews Endocrinology
Further insights into modulation of complement activation by the factor H-related family of proteins - Immunology
Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. - Leibniz-HKI
Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury<...
Proteins17
- Aplha, transcription related growth factors and stimulating factors or repressing nuclear factors are complex subunits of proteins involved in cell differentiation. (gentaur.com)
- Binding sites, especially for complement receptor (CR3), malondialdehyde (MDA)-modified proteins, and apolipoprotein E (apoE), are dispersed throughout its 20 CCP modules (CCPs), also known as short consensus repeats, to facilitate additional 'non-canonical' FH activities. (imedpub.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 regulatory factor I (CFI) is a two-chain serine protease and an endogenous inhibitor of the classical and alternative complement pathways by cleaving C3b and C4b in the presence of cofactor proteins. (discovermednews.com)
- Cell surface proteins have evolved which prevent EC damage by the cytotoxic defence system, decay-accelerating factor (DAF), protectin (CD59) and membrane cofactor protein (MCP). (biomedcentral.com)
- We now show that complement factor H-related protein 1 (FHR-1) and factor H-like protein 1 (FHL-1), proteins of the FH protein family that show amino acid sequence and regulatory function similarities with FH, also bind to Stx2. (leibniz-hki.de)
- The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. (medlineplus.gov)
- Complement factor I and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed. (medlineplus.gov)
- C3 and factor B proteins were measured in culture supernatant by enzyme-linked immunosorbent assay and C3 and factor B transcripts in harvested cells by reverse transcriptase - polymerase chain reaction . (bvsalud.org)
- Cytokine induced upregulation of C3 and factor B proteins was always associated with the upregulation of levels of C3 and factor B mRNA . (bvsalud.org)
- This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). (ox.ac.uk)
- thus, PIGA mutations lead to a deficiency of GPI-anchored proteins, such as complement decay-accelerating factor (also known as CD55) and CD59 glycoprotein (CD59), which are both complement inhibitors. (medscape.com)
- Genes that encode the proteins of complement components or their isotypes are distributed throughout different chromosomes, with 19 genes comprising 3 significant complement gene clusters in the human genome. (medscape.com)
- The important components of this system are various cell membrane-associated proteins such as complement receptor 1 (CR1), complement receptor 2 (CR2), and decay accelerating factor (DAF). (medscape.com)
- for example, the proteins factor H and factor I inhibit the formation of the enzyme C3 convertase of the alternative pathway. (medscape.com)
- Complement dysregulation is usually from a mutation in genes controlling complement proteins or factors but sometimes from acquired autoantibodies to certain complement factors. (msdmanuals.com)
Pathway22
- Factor H binds to C3b, accelerates the decay of the alternative pathway C3-convertase and acts as a cofactor for the factor Imediated proteolyticinac-tivation of C3b. (biovendor.com)
- Factor H (FH) is the primary negative regulator of the alternative pathway (AP) of complement. (ersjournals.com)
- Laboratory features usually include decreased serum levels of factor H , complement component C3 (120700), and a decrease in other alternative pathway components, indicating activation of the alternative complement pathway. (findzebra.com)
- More than 80% of patients with MPGN II are positive for serum C3 nephritic factor (C3NeF), an autoantibody directed against C3bBb, the convertase of the alternative pathway of the complement cascade. (findzebra.com)
- 1987) studied a family in which 3 female sibs had undetectable levels of factor H and C3 nephritic factor, low levels of factor B, C3, and C5 (see 120500), and normal levels of C4-binding protein (120830), factor I (217030), and classic pathway factors. (findzebra.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)
- 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)
- I8/1 antibody recognizes human complement factor D. Complement factor D is a serine protease of the alternative pathway of complement activation.Factor D cleaves factor B bound to C3b, generating the alternative pathway C3 convertase C3bBb and releasing the Ba fragment. (absoluteantibody.com)
- Quantitation of components of the alternative pathway of complement (APC) by enzyme-linked immunosorbent assays. (absoluteantibody.com)
- To test the hypothesis that inflammatory cytokines and complement(C) MACs play a role in the expression of DAF, CD59 and MCP, and to investigate the intracellular signalling pathway involved in DAF expression. (biomedcentral.com)
- It is important in regulating the complement pathway, preventing unnecessary inflammation which can damage the host tissue. (bio-rad-antibodies.com)
- Stx2 was shown to activate complement via the alternative pathway, to bind factor H (FH) at short consensus repeats (SCRs) 6-8 and 18-20 and to delay and reduce FH cofactor activity on the cell surface. (leibniz-hki.de)
- It is widely accepted that members of the complement pathway are expressed at high levels in white adipose tissue (WAT). (nature.com)
- Cellular lysis is counteracted by different cellular defence mechanisms that control this 'tug-of-war' behaviour of the complement system: it can be kept in check or let loose and activate a cell death pathway. (nature.com)
- Upregulation of early and downregulation of terminal pathway complement genes in subcutaneous adipose tissue and adipocytes in acquired obesity. (nature.com)
- Atypical hemolytic uremic syndrome (aHUS) is a disease associated with dysregulation of the immune complement system, especially of the alternative pathway (AP). (elsevierpure.com)
- Factor H is a major plasma protein that plays a critical regulatory role in the alternative pathway of complement activation. (nih.gov)
- and regulation of complement activation, alternative pathway. (jax.org)
- The Response To Alcohol Pathway complements our catalog of research reagents including antibodies and ELISA kits against POMC, ALDH2, AKR1A1, AVP, ADH1B. (novusbio.com)
- In vitro activation of the alternative pathway of complement by settled grain dust. (cdc.gov)
- The complement cascade consists of 3 separate pathways that converge in a final common pathway. (medscape.com)
- Lectins activate the lectin pathway in a manner similar to the antibody interaction with complement in the classical pathway. (medscape.com)
Deficiency14
- Factor I deficiency in turn leads to low levels of complement component 3 (C3), factor B, factor H and properdin in blood, due to unregulated activation of C3 convertase, and to low levels of IgG, due to loss of iC3b and C3dg production. (wikipedia.org)
- Relative FH deficiency was associated with increased factor consumption as evidenced by lower FB and C3 levels and higher Ba:FB and C3a:C3 ratios. (ersjournals.com)
- Conclusions Relative FH deficiency, higher Ba:FB and C3a:C3 ratios, and lower FB and C3 levels suggest a subset of ARDS with complement factor exhaustion, impaired AP function, and increased mortality that may be amenable to therapeutic targeting. (ersjournals.com)
- Complement factor H deficiency (CFHD) can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. (findzebra.com)
- See also complement factor I deficiency (610984), which shows phenotypic overlap with this disorder. (findzebra.com)
- 1982) reported 2 families with partial factor H deficiency and glomerulonephritis. (findzebra.com)
- 1986) reported a consanguineous Algerian family in which 2 brothers had early-onset glomerulonephritis with C3 deposits and low levels (less than 10% of normal) of complement factor H . The factor H deficiency was defined by undetectable complement hemolytic activity by the classic (CH50) and alternate (AP50) pathways, and low levels of C3 and factor B (138470). (findzebra.com)
- 1993) described a consanguineous Italian family in which 3 sibs had deficiency of factor H and its spliced isoform FHL1. (findzebra.com)
- At least 10 mutations in the CFI gene have been identified in people with complement factor I deficiency, a disorder characterized by immune system dysfunction. (medlineplus.gov)
- The lack (deficiency) of functional complement factor I protein allows uncontrolled activation of the complement system. (medlineplus.gov)
- This condition, which may also occur in people with complement factor I deficiency, is characterized by kidney malfunction that can be serious or life-threatening. (medlineplus.gov)
- Baracho GV, Nudelman V, Isaac L. Molecular characterization of homozygous hereditary factor I deficiency. (medlineplus.gov)
- In light of these findings and previous reports of HUS in patients with factor H deficiency, we postulate that abnormalities of factor H may be involved in the etiology of HUS. (nih.gov)
- Cases of complement deficiency have helped defined the role of complement in host defense. (medscape.com)
Protein22
- Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. (wikipedia.org)
- Complement factor I (factor I) is a protein of the complement system, first isolated in 1966 in guinea pig serum, that regulates complement activation by cleaving cell-bound or fluid phase C3b and C4b. (wikipedia.org)
- Then, factor I is cleaved by furin to yield the mature factor I protein, which is a disulfide-linked dimer of heavy chain (residues 19-335, 51 kDalton) and light chain (residues 340-583, 37 kDalton). (wikipedia.org)
- the heavy chain plays an inhibitory role in maintaining the enzyme inactive until it meets the complex formed by the substrate (either C3b or C4b) and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein). (wikipedia.org)
- See the reference protein sequence for complement factor H precursor (NP_569093.2). (nih.gov)
- Complement factor H, a 155 kDaplasma glycoprotein, is an essential regulatory protein that plays a critical role in the homeostasis of the complement system in plasma and in the protection of bystander host cells and tissues from damage by complement activation. (biovendor.com)
- In addition, factor H has multiple physiological activities acts as an extracellularmatrix component, binds to cellular receptors of the integrintype, and interacts with a wide selection of ligands, such as the C-reactive protein, thrombospondin, bone sialoprotein, osteopontin, and heparin. (biovendor.com)
- Complement factor H is a soluble AP suppressor that recognizes self-surfaces on autologous surfaces, either directly via particular glycosaminoglycan and sialic acid or indirectly via C-reactive protein (CRP), and operates in fluid phase. (imedpub.com)
- Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. (leibniz-hki.de)
- Poolpol K, Orth-Höller D, Speth C, Zipfel PF, Skerka C, de Córdoba SR, Brockmeyer J, Bielaszewska M, Würzner R (2014) Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. (leibniz-hki.de)
- The CFI gene provides instructions for making a protein called complement factor I. This protein helps regulate a part of the body's immune response known as the complement system. (medlineplus.gov)
- The unregulated activity of the complement system decreases blood levels of another complement protein called C3, reducing the immune system's ability to fight infections. (medlineplus.gov)
- The CFI gene mutations identified in this disorder result in an abnormal or nonfunctional version of complement factor I. The defective protein allows uncontrolled activation of the complement system. (medlineplus.gov)
- The overactive complement system attacks certain kidney cells, which damages the kidneys and leads to a loss of protein in the urine (proteinuria). (medlineplus.gov)
- Complement factor H (CFH), consisting of 20 domains called complement control protein (CCP1-20), downregulates the AP as a cofactor for mediating C3 inactivation by complement factor I. However, anomalies related to CFH are known to cause excessive complement activation and cytotoxicity. (elsevierpure.com)
- Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi. (ox.ac.uk)
- Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. (ox.ac.uk)
- In an individual with the sporadic/relapsing form of the disease we have found a mutation comprising a deletion, subsequent frame shift and premature stop codon leading to half normal levels of serum factor H. In one of the three families there is a point mutation in exon 20 causing an arginine to glycine change, which is likely to alter structure and hence function of the factor H protein. (nih.gov)
- Eculizumab (Soliris) and ravulizumab-cwvz (Ultomiris) are inhibitors that work to block complement protein C5. (webmd.com)
- There's another complement protein called C6. (webmd.com)
- Protein expression is influenced by many factors that may vary between experiments or laboratories. (genscript.com)
- These bacteria use the surface protein Usp2 to capture and incapacitate the major complement factor C3. (lu.se)
Pathways3
- Activation of the complement pathways. (medscape.com)
- This prevents these components of the classical and of alternative complement pathways from forming a positive feedback loop. (bio-rad-antibodies.com)
- Complement pathways and deficiencies. (medscape.com)
Form a unique fingerprint1
- Dive into the research topics of 'Functional anatomy of complement Factor H'. Together they form a unique fingerprint. (ed.ac.uk)
Cascade9
- 2006) summarized features of MPGN relevant to the complement cascade. (findzebra.com)
- The complement system functions as an interactive sequence, with one reaction leading to another in the form of a cascade. (medscape.com)
- Mutations in the CFI gene result in an inability to control the complement cascade appropriately. (discovermednews.com)
- How the immune response can activate the cascade process is still unknown but it is proposed to act in synergy with additional exacerbating factors such as predisposing maternal and ambient factors [ 12 ]. (hindawi.com)
- Genetic studies have strongly supported a relationship between the alternative complement cascade, in particular the common H402 variant in Complement Factor H (CFH) and development of AMD. (johnshopkins.edu)
- mouse homolog is a regulatory serine proteinase of the complement cascade that cleaves C3b and C4b and inactivates them [RGD, Feb 2006]. (genscript.com)
- The effects of settled grain dust on the human serum complement cascade were investigated. (cdc.gov)
- Deficiencies in the complement cascade can lead to overwhelming infection and sepsis. (medscape.com)
- New studies point to the complex interplay between the complement cascade and adaptive immune response, and complement is also being studied in association with ischemic injury as a target of therapy. (medscape.com)
Atypical hemolytic uremic s2
- Atypical hemolytic uremic syndrome is caused by complement overactivation. (wikipedia.org)
- Complement factor B (FB) mutant variants are associated with excessive complement activation in kidney diseases such as atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy and membranoproliferative glomerulonephritis (MPGN). (lu.se)
Antibody9
- Recombinant monoclonal antibody to Complement Factor D. Manufactured using AbAb's Recombinant Platform with variable regions (i.e. specificity) from the hybridoma I8/1. (absoluteantibody.com)
- This antibody was raised by immunizing BALB/c mice with the purified complement factor D and by the subsequent generation of hybridomas. (absoluteantibody.com)
- I8/1 antibody can be used for the identification of the complement factor D from human serum and plasma. (absoluteantibody.com)
- For instance, this antibody was utilized in the quantitation of the factor D levels in blood of patients with renal failure via a senstive ELISA procedure (Oppermann et al. (absoluteantibody.com)
- Immunofluorescence staining of K562 cells with anti-Complement Factor D (Ab01588) I8/1 Immunofluorescence analysis of paraformaldehyde fixed K562 cells on Shi-fix™ coverslips stained with the chimeric rabbit IgG version of I8/1 (Ab01588-23.0) at 10 µg/ml for 1h followed by Alexa Fluor® 488 secondary antibody (2 µg/ml), showing membrane staining. (absoluteantibody.com)
- To study the effect of MAC on HMEC expression of DAF, EC monolayers were opsonised with IgG2a anti-endoglin monoclonal antibody, thus optimising complement fixation ability. (biomedcentral.com)
- Mice were control treated or treated with BB5.1, a monoclonal antibody that prevents cleavage of complement factor C5, thereby preventing C5a generation and formation of the membrane attack complex (MAC). (maastrichtuniversity.nl)
- Mouse anti Human Complement Factor H antibody, clone 028B-244.2.10X (10-10) recognizes human complement factor H which exists in 2 forms. (bio-rad-antibodies.com)
- Interestingly, the most primordial defense responses employed by myeloid cells against pathogens, such as complement activation, antibody-dependent cell cytotoxicity and phagocytosis, actually seem to favor cancer progression. (frontiersin.org)
Cleaves1
- Cellular membrane type-1 matrix metalloproteinase (MT1-MMP) cleaves C3b, an essential component of the complement system. (nature.com)
Role of complement2
- Welch (2002) discussed the role of complement in renal disease. (findzebra.com)
- In conclusion, multiple interactions of key complement inhibitors FH, FHR-1 and FHL-1 with Stx2 corroborate our hypothesis of a direct role of complement in EHEC-associated HUS. (leibniz-hki.de)
Abstract2
- abstract = "Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: inhibition of late apoptosis and inflammation.De Vries B, Matthijsen RA, Wolfs TG, Van Bijnen AA, Heeringa P, Buurman WA.Department of General Surgery, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands.BACKGROUND: Complement has been implicated in the pathophysiology of renal ischemia-reperfusion (I/R) injury. (maastrichtuniversity.nl)
- abstract = "Complement factor C5a acting via C5a receptors (C5aR) is recognized as an anaphylotoxin and chemoattractant that exerts proinflammatory effects in many pathological states. (elsevierpure.com)
Activation of the complement system1
- CONCLUSIONS: Renal I/R is followed by activation of the complement system and intrarenal deposition of C3 and MAC. (maastrichtuniversity.nl)
Inhibitors1
- Conventional protease inhibitors do not completely inactivate Factor I but they can do so if the enzyme is pre-incubated with its substrate: this supports the proposed rearrangement of the molecule upon binding to the substrate. (wikipedia.org)
Serum5
- In 1 family, of Polish origin, a teenaged male had vasculitis, thrombocytopenia, proteinuria, and depressed levels of serum factor H and complement component C3. (findzebra.com)
- The index case had depressed serum factors H and B levels and IgA nephropathy (161950) which progressed to renal failure. (findzebra.com)
- The most widely studied serum markers for PE, to date, are vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). (hindawi.com)
- Factor H is secreted by the liver into the blood serum. (bio-rad-antibodies.com)
- CspA-mediated binding of human factor H inhibits complement deposition and confers serum resistance in Borrelia burgdorferi. (ouhsc.edu)
Mutations5
- Loss of function mutations in the Complement Factor I gene lead to low levels of factor I which results in increased complement activity. (wikipedia.org)
- These results suggest that FD inhibition can effectively block complement overactivation induced by FB gain-of-function mutations. (lu.se)
- The mutations result in abnormal, nonfunctional, or absent complement factor I. (medlineplus.gov)
- Characterization of mutations in complement factor I (CFI) associated with hemolytic uremic syndrome. (medlineplus.gov)
- Subsequent mutation analysis of the factor H gene has revealed two mutations in patients with HUS. (nih.gov)
Immune4
- Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection. (nih.gov)
- The trouble in PNH comes from part of your immune system called the complement system. (webmd.com)
- The complement system is part of the innate immune system. (medscape.com)
- In addition to playing an important role in host defense against infection, the complement system is a mediator in both the pathogenesis and prevention of immune complex diseases, such as systemic lupus erythematosus (SLE). (medscape.com)
Serine1
- The factor I light chain contains only the serine protease domain. (wikipedia.org)
Hemolytic complement1
- Factor-B conversion and reductions in hemolytic complement consumption were dose related. (cdc.gov)
Pathogens3
- This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design. (ox.ac.uk)
- Although the complement system is part of the body's innate, relatively nonspecific defense against pathogens, its role is hardly primitive or easily understood. (medscape.com)
- As a first line of defense against pathogens and a mediator between innate and adaptive immunity, complement is a particular focus of evasion strategies developed by pathogens. (lu.se)
Regulation of complement activation1
- Background Effective regulation of complement activation may be crucial to preserving complement function during ARDS. (ersjournals.com)
Regulators1
- Angiogenic factors and their receptors are important regulators of placental vascular development [ 13 ]. (hindawi.com)
System12
- The complement system is a crucial component of the innate immunity against microbial infection. (biovendor.com)
- Due to the constant monitoring of its alternate channel, the complement system reacts promptly to threat (AP). (imedpub.com)
- The complement system labels microbes and host debris for clearance. (rcsb.org)
- The complement system has recently been found to be involved in the pathogenesis of EHEC-associated HUS. (leibniz-hki.de)
- Adipocytes have high levels of many components of the complement system. (nature.com)
- Up-regulation of the complement system in subcutaneous adipocytes from nonobese, hypertriglyceridemic subjects is associated with adipocyte insulin resistance. (nature.com)
- The complement system plays an important part in host defense and inflammation . (bvsalud.org)
- Researchers are also looking at medicines that work against other players in the complement system. (webmd.com)
- The complement system plays an important part in defense against pyogenic organisms. (medscape.com)
- These findings underscore the duality of the complement system. (medscape.com)
- Knowledge about the complement system is expanding. (medscape.com)
- An intricate system regulates complement activity. (medscape.com)
Adipsin1
- Complement factor D (adipsin) levels are elevated in acquired partial lipodystrophy (Barraquer-Simons syndrome). (nature.com)
Membrane attack3
- The factor I heavy chain has four domains: an FI membrane attack complex (FIMAC) domain, CD5 domain, and low density lipoprotein receptor 1 and 2 (LDLr1 and LDLr2) domains. (wikipedia.org)
- DAF prevents the formation and accelerates the decay of complement 3 (C3) convertases, MCP binds to C3b and C4b promoting their degradation and CD59 inhibits the membrane-attack complex (MAC). (biomedcentral.com)
- We also review the literature on the role of other complement components in AMD pathobiologies, including C3a, C5a and the membrane attack complex (MAC), and on transgenic mouse models developed to interrogate in vivo the effects of the CFH Y402H polymorphism. (johnshopkins.edu)
Inflammation4
- The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy. (nih.gov)
- Complement activation plays a crucial role in the regulation of inflammation and late apoptosis. (maastrichtuniversity.nl)
- 4 , 6 - 9 Several factors, including inflammation, oxidative stress, and dyslipidemia, are considered decisive for the progression of atherosclerosis in ESRD. (lww.com)
- at the same time, the inflammation promoted by complement activation can result in cellular damage when not kept in check. (medscape.com)
Macular Degeneration5
- Complement factor H regulates retinal development and its absence may establish a footprint for age related macular degeneration. (nih.gov)
- Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration. (ox.ac.uk)
- This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT) for age-related macular degeneration (AMD). (dovepress.com)
- Association of single nucleotide polymorphism in complement factor I gene with age-related macular degeneration]. (genscript.com)
- Genetic, behavioral, and sociodemographic risk factors for second eye progression in age-related macular degeneration. (genscript.com)
Heparin1
- Enables complement component C3b binding activity and heparin binding activity. (jax.org)
Tumor necro2
- Human keratinocytes were cultured in the presence of supernatant of activated peripheral blood mononuclear cells , interleukin-1alpha , interleukin-2 , interleukin-6 , transforming growth factor-beta1 , tumor necrosis factor-alpha , or interferon-gamma . (bvsalud.org)
- Tumor necrosis factor-alpha induced production of C3 and interferon-gamma induced production of factor B were inhibited by cycloheximide . (bvsalud.org)
Receptor1
- Similarly, sEng is a truncated form of receptor for two subtypes of transforming growth factor beta (TGF β ) specifically, TGF β 1 and TGF β 2 which are highly expressed by vascular endothelial cells and syncytiotrophoblasts. (hindawi.com)
Properdin1
- Exceptions are C1, factor D, and properdin. (medscape.com)
Pathophysiology1
- BACKGROUND: Complement has been implicated in the pathophysiology of renal ischemia-reperfusion (I/R) injury. (maastrichtuniversity.nl)
Damage by complement1
- How do endothelial cells (ECs) protect themselves against damage by complement, particularly when they are present at the interface between blood and inflamed tissue? (biomedcentral.com)
Cleavage2
- Mutagenesis was performed to study the effect of factor D (FD) inhibition on C3 convertase-induced FB cleavage, complement-mediated. (lu.se)
- Complement factor H functions as a cofactor in the inactivation of C3b by factor I. It makes C3b susceptible to cleavage by factor I, resulting in iC3b. (bio-rad-antibodies.com)
MRNA1
- Rattus norvegicus complement factor I (Cfi), mRNA. (genscript.com)
Renal diseases2
- Complement factor H has revealed an association with two different renal diseases, glomerulonephri-tisand atypical hemolytic uremicsyndrome (aHUS). (biovendor.com)
- Patients with aHUS are currently treated with eculizumab while there is no specific treatment for other complement-mediated renal diseases. (lu.se)
Cytokines4
- This in turn results in an exponential production of multiple factors such as cytokines and growth factors leading to the clinical manifestations of PE [ 11 ]. (hindawi.com)
- Synthesis of complement components C3 and factor B in human keratinocytes is differentially regulated by cytokines. (bvsalud.org)
- In skin the keratinocyte is the major cell type, it is known to produce two soluble complement components, C3 and factor B . In this study we investigated the regulation of synthesis of these components in foreskin keratinocytes by cytokines . (bvsalud.org)
- In conclusion, synthesis of C3 and factor B in keratinocytes is regulated by some cytokines , known to be produced by inflammatory cells and keratinocytes . (bvsalud.org)
Human4
- Crystal structure the crystal structure of human Factor I has been deposited as PDB: 2XRC. (wikipedia.org)
- Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after xenotransplantation to nonhuman primates. (elsevierpure.com)
- Orthologous to human CFH (complement factor H). (jax.org)
- Another important mechanism by which bacteria resist human complement is the production of proteases that efficiently degrade complement components. (lu.se)
C3bBb1
- Factor H also inhibits the formation of the C3bBb complex (C3 convertase) and increases the rate of dissociation of both C3 convertase and the (C3b)NBB complex (C5 convertase). (bio-rad-antibodies.com)
Humans1
- The gene for Factor I in humans is located on chromosome 4. (wikipedia.org)
Bind1
- We showed that one common strategy is to bind complement inhibitor C4BP, which leads to decreased opsonisation of bacteria with C3b impairing phagocytosis and allowing bacterial survival. (lu.se)
Component1
- The authors then performed a complement analysis, which revealed that component concentrations and factor levels were normal. (discovermednews.com)
Diseases2
- In addition to the following diseases, low factor I is associated with recurrent bacterial infections in children. (wikipedia.org)
- [ 3 ] A registry of complement deficiencies has been established as a means to promote joint projects on treatment and prevention of diseases associated with defective complement function. (medscape.com)
Inhibition1
- Furthermore, we examined the effect of inhibition of complement-factor C5 on renal I/R injury. (maastrichtuniversity.nl)
Binds1
- Here, C3b binds to factor B that is cleaved by factor D to Bb. (medscape.com)
20001
- The complement facts book , San Diego, 2000. (medscape.com)
ELISA1
- Factor B (FB) and FH levels were quantified by ELISA using samples from the ARDSnet LARMA and SAILS (N=224) trials. (ersjournals.com)
Manifestations1
- He was found to have a rare heterozygous mutation in the complement factor I gene (CFI) that was not previously associated with neurologic manifestations. (discovermednews.com)