complement pathways

complement pathways

1. the classical complement pathway (initiated usually by binding of C1 to IgG or IgM antibody to C1) is a complex of three subunits: C1q, C1r, and C1s. After C1q is bound, C1r (an overbar indicates enzymatic activity) cleaves C1s to C1s. C1s cleaves both C4 into C4a and C4b as well as C2 into C2a and C2b. C2b combines with C4b to form C4b2b, which is a C3 convertase. C3 convertase cleaves C3 into C3a and C3b. C3b joins C4bC2b to form a C5 convertase (also known as C4b2b3b), which cleaves C5 into C5a and C5b. After C5b has been bound to the cell surface, the remainder of the complement components (C6-C9) as well as C5b form the membrane attack complex (MAC). MAC causes a hole in the cell membrane.
2. in the alternative complement pathway, surface-bound C3b binds factor B, which is cleaved by factor D into Ba and Bb. C3bBb is an unstable C3 convertase unless properdin (P) binds to it to form C3bBbP. The stable C3 convertase generates more C3b. When a complex of C3bBbC3b is formed, this is the alternative pathway C5 convertase. From C5b through C9, the classical and alternative pathways are the same.
3. In the lectin-binding pathway, mannose-binding protein initiates the pathway, which then uses components of the classical complement pathway. Some of the "a" components of both pathways have various biologic activities, that is, C3a is an anaphylatoxin.

com·ple·ment path·ways

(kom'plĕ-mĕnt path'wāz)
1. The classical complement pathway (initiated usually by binding of C1 to IgG or IgM antibody to C1) is a complex of three subunits: C1q, C1r, and C1s. After C1q is bound, C1r (an overbar indicates enzymatic activity) cleaves C1s to C1s. C1s cleaves both C4 into C4a and C4b as well as C2 into C2a and C2b. C2b combines with C4b to form C4b2b, which is a C3 convertase. C3 convertase cleaves C3 into C3a and C3b. C3b joins C4bC2b to form a C5 convertase (also known as C4b2b3b), which cleaves C5 into C5a and C5b. After C5b is bound to the cell surface the remainder of the complement components (C6-C9) as well as C5b form the membrane attack complex (MAC). MAC causes a hole in the cell membrane.
2. In the alternative complement pathway, surface-bound C3b binds Factor B, which is cleaved by Factor D into Ba and Bb. C3bBb is an unstable C3 convertase unless properdin (P) binds to it to form C3bBbP. The stable C3 convertase generates more C3b. When a complex of C3bBbC3b is formed, this is the alternative pathway C5 convertase. From C5b through C9, the classical and alternative pathways are the same.
3. In the lectin-binding pathway, mannose-binding protein (MBP) initiates the pathway, which then uses components of the classical complement pathway. Some of the "a" components of both pathways have various biologic activities, i.e., C3a is an anaphylatoxin.
References in periodicals archive ?
Second, the clinician could be looking for consumption, where an over-activation of complement pathways results in low levels of complement proteins.
A likely hypothesis is that increased release of C3 breakdown products in sepsis facilitates clearance of amyloid and tau proteins leading to diminished activation of alternative and classical complement pathways.
By targeting C3, the point of convergence of all three complement pathways , Apellis believes APL-2 has the potential to eliminate the excessive and inappropriate C3 activation that is central to C3G, thereby avoiding glomerular C3 deposition and progression of renal disease.
The alternative and classical complement pathways were suppressed confirming drug action (CH50 and AP50 hemolytic assays < 10%).
In this study therefore, we isolated and purified a new water-soluble polysaccharide from the S3 fraction of SJZD prescription, characterized its structure, and investigated the potential activity of this polysaccharide against classical complement pathways. The results of this study will offer a theoretical basis for further investigation on the structure-activity relationship and development of SJZD polysaccharides.
We show here that the venom can activate all three Complement pathways (Figure 1).
POT-4, now known as AL-78898A (Alcon), is a cyclic peptide that irreversibly binds to C3 to inhibit complement pathways and prevent membrane attack complex formation.
Three different complement pathways have been defined: the classical, alternative, and lectin pathways.
Several genetic causes of aHUS have been identified including those that affect complement pathways and B12 metabolism.
For example, lipopolysaccharide of Mycoplasma species interacting with C1 and inducing an antibody-independent activation of the complement system via the classical pathway (Bredt et al., 1977; Rosendal et al., 1994), Epstein-Barr-Viruses activating both complement pathways (Mayes et al., 1984; Mold et al., 1988), vaccination affecting acute phase response through cytokines like interleukin-1 (IL1), IL6, and transforming growth factor beta 1 (TGFB1) that are released during immune response and, in particular, trigger the complement activity (Castell et al., 1989; Mackiewicz et al., 1990; Gonzalez-Ramon et al., 2000).
A clear decrease at the serum levels or complete absence of complement factors or complement regulatory proteins alter the different complement pathways.Several clinical complications are summarized including the complement pathway involved, the deficient complement factor and the clinical manifestation associated.

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