• Glycans, either alone or complexed with glycan-binding proteins, can deliver intracellular signals or control extracellular processes that promote initiation, execution and resolution of cell death programs. (nature.com)
  • Herein, we review the role of glycans and glycan-binding proteins as essential components of the cell death machinery during physiologic and pathologic settings. (nature.com)
  • At that time, glycobiology, which is the study of carbohydrates and their recognition by motif-specific carbohydrate-binding proteins or lectins, lagged far behind the studies that defined the structural and cellular biology of cell death. (nature.com)
  • The complement system consists of a number of small proteins found in the blood, normally circulating as inactive zymogens . (wikidoc.org)
  • There are proteins with modules similar in overall structure to CRDs that serve functions other than sugar binding. (embl.de)
  • Lectins are a diverse group of proteins, both in terms of structure and activity. (embl.de)
  • When examined from the viewpoint of the bound sugar, the structural information accumulated so far on lectins and other proteins that are specific to galactose and glucose (or mannose), provides suggestive evidence for distinct ligand-dependent distribution of hydrogen-bond partners in the combining site. (embl.de)
  • Activation of the complement system in response to an infection or foreign antigen is achieved via three complement pathways, the classical pathway, which is activated by antigen-antibody complexes, the lectin pathway, which is activated by the interaction of microbial carbohydrates with mannose-binding proteins in the plasma and tissue fluids, and the alternative complement pathway, which is activated by C3b binding to microbial surfaces and to antibody molecules. (hindawi.com)
  • It is derived from many small plasma proteins that form the biochemical cascade of the immune system. (dadamo.com)
  • The complement system consists of more than 35 soluble and cell-bound proteins, 12 of which are directly involved in the complement pathways. (dadamo.com)
  • Mannose-binding lectin (MBL) and MBL-associated serine proteases 2 (MASP-2) are important proteins in the lectin pathway of the immune system. (biomedcentral.com)
  • In a cascade of proteolytic cleavage events, MASP-2 activates complement proteins C4 and C2 to form C4b2a (classical C3 convertase), thereby converging the lectin pathway with the classical pathway of complement activation. (escholarship.org)
  • Further, MASP-2 activity is regulated by several factors, including the serine protease inhibitor C1INH and by interaction with other proteins of the lectin complement pathway. (escholarship.org)
  • We have previously shown that hemocyanins are internalized by APCs through receptor-mediated endocytosis with proteins that contain C-type lectin domains, such as mannose receptor (MR). However, the contribution of other innate immune receptors to the proinflammatory signaling pathway triggered by hemocyanins is unknown. (exeter.ac.uk)
  • The article mentions, "Complement activation may occur early during SARS-CoV-2 infection by the direct interaction of viral proteins with mannose- binding lectin and ficolin pathway. (acquaintpublications.com)
  • Three biochemical pathways activate the complement system: the classical complement pathway , the alternative complement pathway , and the mannose-binding lectin pathway . (wikidoc.org)
  • The classical complement pathway typically requires antibodies for activation (specific immune response), while the alternative and mannose-binding lectin pathways can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). (wikidoc.org)
  • The classical pathway is triggered by activation of the C1-complex (which consists of one molecule C1q and two molecules C1r and C1s), either by C1q's binding to antibodies from classes M and G, complexed with antigens , or by its binding C1q to the surface of the pathogen. (wikidoc.org)
  • According to research findings, after the pathogenic microorganism invades the body, mannose-binding lectin (MBL) binds with mannan residues on its surface, and activate MBL-associated serine Proteases (MASPs) and the lectin pathway of the complement system, generating non-specific immune responses [ 8 , 9 ]. (biomedcentral.com)
  • The classical, lectin, and alternative pathways converge into a final common pathway when C3 convertase (C3 con) cleaves C3 into C3a and C3b. (msdmanuals.com)
  • The viral nucleocapsid protein binds to a mannose-binding protein-associated serine protease 2 (MASP-2), a key protease of the MBL pathway leading to overactivation of the complement system and worsening of lung injury. (acquaintpublications.com)
  • Based on the expression of CD206 mannose receptors on disease-associated macrophages, BIND and Macrophage plan to conduct joint research to develop a CD206 targeted Accurin nanoparticle that is capable of concentrating various therapeutic payloads to the tumor microenvironment. (businesswire.com)
  • According to this theory, the immune system consists of cells which have specific receptors on their surface to recognize antigens. (wikidoc.org)
  • These receptors, which we now call "antibodies", were called by Ehrlich "amboceptors" to emphasize their bifunctional binding capacity: they recognize and bind to a specific antigen, but they also recognize and bind to the heat-labile antimicrobial component of fresh serum. (wikidoc.org)
  • Adherent receptors mediate adherence of cells and other particles with bound C3b or C4b fragments and are known as CR1 to CR5. (dadamo.com)
  • These receptors, present on the other cells of the immune system, are involved in a variety of immunoregulatory reactions. (dadamo.com)
  • These complexes serve as pathogen receptors, which are further bound to MASP-1 , a serine protease. (escholarship.org)
  • The immune system utilizes sensors on immune cells named pattern recognition receptors to recognize invading pathogens and foreign substances. (exeter.ac.uk)
  • These receptors trigger a plethora of immune responses that confer protection against infection and could also contribute to unwanted exacerbated immune responses. (exeter.ac.uk)
  • In the Brown Group, we are interested in a superfamily of receptors called C-type lectin receptors (CLRs). (exeter.ac.uk)
  • However, we know very little of how these receptors, in particular Dectin-1, influences adaptive immune responses to fungi. (exeter.ac.uk)
  • Griffithsin's antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. (mdpi.com)
  • Finally, using biotinylated high-mannose N-glycans, Grün et al. (biosyn.com)
  • MASP-2 (mannose/mannan binding lectin (MBL) associated serine protease-2) is a serum protein predominantly synthesized by the liver as a ~75kDa protein and is one of the key molecules of the innate immune system. (escholarship.org)
  • Two decades later, pioneering studies suggested that lectin-like molecules constitutively expressed on the surface of macrophages can selectively recognize changes on glycans decorating the surface of apoptotic thymocytes, 4 , 5 although these studies likewise did not provide substantial insight into the mechanisms by which lectin-glycan interactions regulate cell death. (nature.com)
  • Overview of the Immune System The immune system distinguishes self from nonself and eliminates potentially harmful nonself molecules and cells from the body. (msdmanuals.com)
  • The emergence of functional studies on animal lectins during the 1990s has provided the appropriate framework to better understand their roles in cell death. (nature.com)
  • Immune system abnormalities may be caused partly by complement system factor I deficiency. (hindawi.com)
  • Complement C3b is the major opsonin of the complement system which facilitates the phagocytosis process by coating antigens (each of the phagocytes expresses a complement receptor such as CR1, CR3, or CR4 that binds C3b, C4b, or C3bi) [ 28 , 29 ]. (hindawi.com)
  • Protein MASP-2 and MAp19 encoded by MASP-2 genes both can bind with MBL, generate MBL-MASP compound, and then activate C4-C9 components in the complement system, generating membrane attack complex and opsonin as well as other inflammatory cytokines promoting the killing of pathogenic microorganisms [ 10 , 11 ]. (biomedcentral.com)
  • The complement system is an integral part of the innate immune system but also augments adaptive immune responses. (wjgnet.com)
  • The complement system is a tightly regulated, cascading protein network representing a key component linking the innate and humoral immune systems. (jrheum.org)
  • The complement system is a tightly regulated, cascading protein network that performs multiple roles in homeostasis and disease prevention and is a key component of both the innate and the humoral immune systems. (jrheum.org)
  • Activation of the complement system occurs through the classical (CP), lectin (LP), or alternative (AP) pathways. (jrheum.org)
  • Per Richard Stienm [1] , on UpToDate, the complement system plays a vital role in instructing the adaptive immune response and removal of damaged cells, tissue regeneration, and angiogenesis. (acquaintpublications.com)
  • The antibodies which the immune system generates against the M protein may cross-react with heart muscle cell protein myosin, heart muscle glycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction. (wikipedia.org)
  • The CCR5 co-receptor also binds with chemokines produced by CD8+ T cells, including RANTES (CCL5), and MIP (macrophage inflammatory protein) 1α (CCL3) and 1β (CCL4). (biomedcentral.com)
  • Relatively low affinity binding sites for monosaccharides are formed at shallow indentations on protein surfaces. (embl.de)
  • Higher selectivity of binding is achieved by extending binding sites through additional direct and water-mediated contacts between oligosaccharides and the protein surface. (embl.de)
  • Factor I cleaves C3b and C4b in a reaction, where fI is dependent on various cofactors, such as factor H, C4b-binding protein CR1 and membrane cofactor protein (MCP) [ 26 ]. (hindawi.com)
  • It is mainly bound to multimeric protein complexes, such as MBL , the three ficolins ( M-ficolin , L-ficolin and H-ficolin ) and collectin kidney 1 (CL-K1, alias CL-11). (escholarship.org)
  • Mannose binding lectin (MBL) is a liver derived protein which plays an important role in innate immunity. (springeropen.com)
  • One nsSNP Gly54Asp (rs1800450) was found to be deleterious and damaging by both SIFT and Polyphen-2 servers and thus affecting MBL2 protein stability and expression. (springeropen.com)
  • Mannose binding lectin (MBL) is a liver derived acute phase protein. (springeropen.com)
  • it occurs when mannose-binding lectin (MBL), a serum protein, binds to mannose, fucose, or N -acetylglucosamine groups on bacterial cell walls, yeast walls, or viruses. (msdmanuals.com)
  • Endogenous lectins and glycans are critical signals in the resolution of cell death. (nature.com)
  • Although lectins were already known because of their ability to agglutinate red blood cells, 3 the involvement of lectins and glycans in PCD had not been elucidated. (nature.com)
  • The research group demonstrated that biotinylated glycans enable the production of glycan arrays to determine specific interactions of lectins. (biosyn.com)
  • Furthermore, the study showed that fluorescent beads coated with selected biotinylated glycans bind to dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN)-expressing dendritic cells in vitro. (biosyn.com)
  • In the late 19th century, blood serum was found to contain a "factor" or "principle" which was capable of killing bacteria. (wikidoc.org)
  • The heat-stable component was found to confer immunity against specific microorganisms, while the heat-labile component was found to be responsible for the non-specific antimicrobial activity conferred by all normal serum. (wikidoc.org)
  • C3b binds to the surface of pathogens leading to greater internalization by phagocytic cells by opsonization . (wikidoc.org)
  • When the epithelial cells are initially damaged, the body produces an immune response - sending in neutrophils and monocytes in to kill the pathogens. (geneticlifehacks.com)
  • It binds to carbohydrates on the surface of mannose-rich pathogens and mediates clearing by phagocytosis or complement activation (Nepomuceno et al. (springeropen.com)
  • We confirmed a glycan-dependent binding of hemocyanins to chimeric TLR4 in vitro. (exeter.ac.uk)
  • CAMBRIDGE, Mass. & DUBLIN, Ohio--( BUSINESS WIRE )--BIND Therapeutics, Inc. (NASDAQ: BIND), a clinical-stage nanomedicine company developing targeted and programmable therapeutics called Accurins™, and Macrophage Therapeutics, a subsidiary of Navidea Biopharmaceuticals, Inc. (NYSE: NAVB) today announced they have entered into a research collaboration to engineer Accurins with the Manocept™ targeting platform that enables selective, efficient binding to CD206 positive disease-associated macrophages. (businesswire.com)
  • We are pleased to work with BIND Therapeutics to explore the therapeutic potential of our two complementary technology platforms," said Michael M. Goldberg, M.D., CEO of Macrophage Therapeutics and Director of Navidea. (businesswire.com)
  • Lectins can be found in many organisms and are involved in a multitude of cellular processes that depend on specific recognition of complex carbohydrates. (embl.de)
  • This collaboration represents a potentially significant advance in the evolution of our platform as we develop Accurins with novel targeting ligands," said Andrew Hirsch, president and chief executive officer of BIND Therapeutics. (businesswire.com)
  • Binding of these complexes to their appropriate pathogenic ligands auto-activates MASP-1. (escholarship.org)
  • Mediators of TMA syndromes overlap with those released in cytokine storm, suggesting close connections between ineffective immune responses to SARS-CoV-2, severe pneumonia and life-threatening microangiopathy. (nature.com)
  • Overall, it is shown that PNP hydrogels elicit improved anti-COVID immune responses with only a single administration, demonstrating their potential as critical technologies to enhance overall pandemic readiness. (uw.edu)
  • Mollusk hemocyanins have biomedical uses as carriers/adjuvants and nonspecific immunostimulants with beneficial clinical outcomes by triggering the production of proinflammatory cytokines in antigen-presenting cells (APCs) and driving immune responses toward type 1 T helper (Th1) polarization. (exeter.ac.uk)
  • As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. (frontiersin.org)
  • This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. (frontiersin.org)
  • Chronic inflammation over the years results in altered immune responses and increases risk of tumor formation and progression. (metabiom.org)
  • convert a subpopulation of #Listeria -infected MDSCs into an immune-stimulating phenotype that produces interleukin-12 (IL-12), a cytokine linked with heightened T cell and NK cell responses. (metabiom.org)
  • CR1 on erythrocytes may bind circulating immune complexes (that had activated complement) and transport them to the liver where the immune complexes are partially degraded and thus become more soluble. (dadamo.com)
  • One mechanism of cell entry involves HIV-1 binding with the CD4 receptor and co-receptor chemokine (CC motif) receptor 5 (CCR5). (biomedcentral.com)
  • Injectable polymer-nanoparticle (PNP) hydrogels are leveraged as a depot technology for the sustained delivery of a nanoparticle antigen (RND-NP) displaying multiple copies of the SARS-CoV-2 receptor-binding domain (RBD) and potent adjuvants including CpG and 3M-052. (uw.edu)
  • Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. (uw.edu)
  • We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophusalcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. (uw.edu)
  • Griffithsin (GRFT), an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. (mdpi.com)
  • Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. (frontiersin.org)
  • How do C-type lectins tailor adaptive immunity following phagocytosis of apoptotic cells? (nature.com)
  • Intracellular lectins and glycan-modifying enzymes mediate autophagy and control host immunity and inflammation. (nature.com)
  • Complement activation occurs in progressive chronic kidney disease and may contribute to the chronic inflammation that is characteristically found in the kidney. (wjgnet.com)
  • We discuss here the contribution of glycan-lectin interactions to the initiation, execution and resolution of apoptosis and their emerging roles in other cell death programs including autophagy. (nature.com)
  • Lectin-carbohydrate interactions: different folds, common recognition principles. (embl.de)
  • This is the second wave of damage that occurs in the lungs, due to our own immune response. (geneticlifehacks.com)
  • Understanding the function of lectin-glycan recognition systems in cell death will facilitate the implementation of novel therapeutic strategies aimed at controlling unbalanced cell proliferation and survival in several pathologic conditions. (nature.com)
  • This domain, which is known as the C-type lectin domain (CTL) or as the carbohydrate-recognition domain (CRD), consists of about 110 to 130 residues. (embl.de)
  • Structural basis of lectin-carbohydrate recognition. (embl.de)
  • Lectins are responsible for cell surface sugar recognition in bacteria, animals, and plants. (embl.de)
  • Our data showed the involvement of TLR4 in the hemocyanin-mediated proinflammatory response in APCs, which could cooperate with MR in innate immune recognition of these glycoproteins. (exeter.ac.uk)
  • In a rapidly evolving pandemic affected by the spread of immune-escaping variants, there is an urgent need to develop vaccines capable of providing robust and durable immunity. (uw.edu)
  • Mannose binding lectin gene 2 ( MBL2 ) polymorphisms are reported to be associated with various diseases. (springeropen.com)
  • Out of these, 4 SNPs from 3′ UTR were found to play role in miRNA binding, 7 SNPs from 5′ near and intronic region were predicted to involve in transcription factor binding and expression of MBL2 gene. (springeropen.com)
  • Factor I deficiency can be conferred by a C3 deficiency, since this also increases susceptibility to pyogenic infections by Neisseria meningitides, Haemophilus influenza, and Streptococcus pneumonia and increases the incidence of immune complex diseases due to impaired complement-mediated function [ 30 ]. (hindawi.com)
  • The term "chemical mediators" encompasses a wide array of substances found in various body fluids and tissues throughout the body. (libretexts.org)
  • CD 11a/CD 18 are found on neutrophils, monocytes, macrophages, and lymphocytes, while VLA-4 is found on monocytes and lymphocytes. (medscape.com)
  • The elegant and novel design of Accurins allow for prolonged circulation, controlled and tunable release and selective targeting of a therapeutic payload to diseased tissue or cells while avoiding immune surveillance detection and systemic toxicities. (businesswire.com)
  • reperfusion protocol, Ncx-6550 and pravastatin were tested only at 22.4 μmol/kg i.p. being given either one hour prior to ischemia (prophylactic protocol) find more or one hour into reperfusion (therapeutic protocol). (gsk-3signals.com)
  • Their mechanisms include maintaining physicochemical conditions in the colon (e.g., pH and bile acid profile), balancing the quantity of beneficial gut microbiota members through the production of short-chain fatty acids, reducing the abundance of putrefactive bacteria producing enzymes such as azoreductase, β-glucosidase, β-glucuronidase, and nitroreductase, binding and degrading mutagenic compounds, as well as performing immunomodulatory activities. (metabiom.org)
  • Unfortunately, a broadened and lengthened immune response can become destructive to the host, triggering concomitant tissue damage and incitement of coagulation. (nature.com)
  • In ARDS, the epithelial cells lining the alveoli no longer remain tightly bound together, allowing them to fill with fluid that leaks in from surrounding tissue. (geneticlifehacks.com)
  • The human immune system derives an extraordinary diversity from the process of reproduction, whereby random reassortment of countless genetic variables forms infinite numbers of unique host defence formulations. (nature.com)
  • Upon achievement of proof-of-concept, the companies anticipate expanding the collaboration to develop Manocept-linked Accurins as a novel, potent approach to impact the tumor microenvironment which, in many forms of cancer, is a barrier to immune effector cells. (businesswire.com)
  • Disease-associated macrophages generally play a pro-tumoral role and are immunosuppressive, preventing the immune system from mounting an attack on tumor cells. (businesswire.com)
  • They are expressed on endothelial cells and bind to the integrins CD 11a/CD 18 (lymphocyte function-associated antigen-1) and VLA-4, respectively. (medscape.com)
  • Ehrlich therefore named this heat-labile component "complement", because it is something in the blood which "complements" the cells of the immune system. (wikidoc.org)
  • Find support for a specific problem in the support section of our website. (mdpi.com)
  • Many of these domains function as calcium-dependent carbohydrate binding modules. (embl.de)