Complement Function in the Neonate
The complement cascade consists of 18 plasma proteins which upon activation regulate the inflammatory response, effect bacteriolysis, solubilize immune complexes, and opsonize microorganisms. Activation of the complement cascade may occur via the antibody-dependent classical pathway (C1, C2, and C4) or the antibody-independent alternative pathway (factor B and factor D) (Arnaout 1985; Pangburn 1983; Reid 1981). Activation of early acting components of both pathways occurs by limited proteolysis. Complexing of a single dimer of IgG or IgM with antigen on cell surfaces activates a single C1 molecule (Borsos 1965). Two subcomponents of C1, C1r and CIs, are sequentially activated, and CIs activates C4 and C2 by limited proteolytic cleavage. An unstable enzyme complex is formed between cleavage fragments of C4 and C2, C4b2a, which activates C3 by cleavage of a 9-kD fragment from the alpha chain of C3. A C3-converting enzyme which cleaves C3 at the same site can also be generated via the alternative pathway (Pangburn 1983). Factor B is a peptide structurally and functionally similar to C2. It is cleaved after complexing with C3b by factor D, a serine protease analogous to CIs. The alternative pathway C3 convertase (C3bBb) is a complex of the 70-kD activation product of factor B, Bb, and C3b. Because the larger activation product of C3, C3b, is part of this complex, a positive amplification loop is established. Activation of C3 by either pathway results in sequential activation of the terminal components C5-C9 and in deposition of C3b, the major activation product of C3, on cell surfaces.
KeywordsPermeability Migration Carbohydrate Superoxide Polysaccharide
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- Arnaout MA, Colten HR (1985) Complement C3 receptors, structure and function. Mol Immunol, in press.Google Scholar
- Colten HR, Silverstein AH, Borsos T (1968b) Ontogeny of the first component of sheep complement. Immunol 15: 459–461.Google Scholar
- Day NKB, Pickering RJ, Gewurz H (1969) Ontogenetic development of the complement system. Immunol 16: 319–325.Google Scholar
- Gitlin D, Biasucci A (1969) Development of gamma-G, gamma-A, gamma-M, beta-1-c/beta-1-a, C’l esterase inhibitor, ceruloplasmin, transferrin, hemopexin, haptoglobin, fibrinogen, plasminogen, alpha-1-antitrypsin, orosomucoid, beta-lipoprotein, alpha-2-macroglobulin, and prealbumin in the human conceptus. J Clin Invest 48: 1433–1446.PubMedCrossRefGoogle Scholar
- Hugli TE (1981) The structural basis for anaphylatoxin and chemotactic functions of C3a, C4a, and C5a. CRC Crit Rev Immunol 1: 321–366.Google Scholar
- Johnston RB, Alterburger KM, Atkinson AW, Curry RH (1979) Complement in the newborn infant. Pediatrics [Suppl] 64: 781–786.Google Scholar
- Kohler PF (1968) Quantitative comparison of complement in the mother and newborn. Fed Proc 27: 491–492.Google Scholar
- Stossel TP, Alper CA, Rosen FS (1973) Opsonic activity in the newborn: role of properdin. Pediatr 52: 134–137.Google Scholar
- Strunk RC, Whitehead AS, Cole FS (1985) Pretranslational regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopoly-saccharide. J Clin Invest (in press)Google Scholar