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.