Complement Function in the Neonate

  • F. Sessions Cole
Conference paper


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.


Permeability Migration Carbohydrate Superoxide Polysaccharide 


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  1. Adamkin D, Stitzel A, Urmson J (1978) Activity of the alternative pathway of complement in the newborn infant. J Pediatr 93: 604–608.PubMedCrossRefGoogle Scholar
  2. Adinolfi M, Gardner B (1967) Synthesis of beta-1-e and beta-1-c components of complement in human fetuses. Acta Paediatr Scand 56: 450–457.PubMedCrossRefGoogle Scholar
  3. Adinolfi M, Gardner B, Wood CBS (1968) Ontogenesis of two components of human complement: beta-1-e and beta-1-c/beta-1-a globulins. Nature 219: 189–190.PubMedCrossRefGoogle Scholar
  4. Adinolfi M (1970) Levels of two components of complement (C4 and C3) in human fetal and neonatal sera. Dev Med Child Neurol 12: 306–313.PubMedCrossRefGoogle Scholar
  5. Adinolfi M, Beck SE (1975) Human complement C7 and C9 in fetal and newborn sera. Arch Dis Child 50: 562–564.PubMedCrossRefGoogle Scholar
  6. Adinolfi M, Dobson NC, Bradwell AR (1981) Synthesis of two components of human complement, beta-1-H and C3bINA, during fetal life. Acta Paediatr Scand 70: 705–712.PubMedCrossRefGoogle Scholar
  7. Alper CA, Rosen FS (1976) Genetics of the complement system. Adv Hum Genet 7: 141–188.PubMedGoogle Scholar
  8. Arnaout MA, Colten HR (1985) Complement C3 receptors, structure and function. Mol Immunol, in press.Google Scholar
  9. Ballow M, Fang F, Good RA (1974) Developmental aspects of complement components in the newborn. Clin Exp Immunol 18: 257–270.PubMedGoogle Scholar
  10. Borsos T, Rapp HJ (1965) Complement fixation on cell surfaces by 19S and 7S antibodies. Science 150: 505.PubMedCrossRefGoogle Scholar
  11. Cole FS, Schneeberger EE, Lichtenberg NA, Colten HR (1982) Complement biosynthesis in human breast milk macrophages and blood monocytes. Immunology 46: 429–443.PubMedGoogle Scholar
  12. Cole FS, Matthews WJ, Rossing RH, Shotola NA, Gash DJ, Pennington JE (1983) Complement biosynthesis by human bronchoalveolar macrophages. Clin Immunol Immunopathol 27: 153–159.PubMedCrossRefGoogle Scholar
  13. Cole FS, Auerbach HS, Goldberger G, Colten HR (1985) Tissue specific pretranslational regulation of complement production in human mononuclear phagocytes. J Immunol 134: 2610–2616.PubMedGoogle Scholar
  14. Colten HR, Gordon JM, Borsos T, Rapp HJ (1968a) Synthesis of the first component of human complement in vitro. J Exp Med 128: 595–616.PubMedCrossRefGoogle Scholar
  15. Colten HR, Silverstein AH, Borsos T (1968b) Ontogeny of the first component of sheep complement. Immunol 15: 459–461.Google Scholar
  16. Colten HR (1972) Ontogeny of the human complement system: in vitro biosynthesis of individual complement components by fetal tissues. J Clin Invest 51: 725–750.PubMedCrossRefGoogle Scholar
  17. Colten HR (1973) Biosynthesis of the fifth component of complement (C5) by human fetal tissues. Clin Immunol Immunopathol 1: 346–352.PubMedCrossRefGoogle Scholar
  18. Day NKB, Pickering RJ, Gewurz H (1969) Ontogenetic development of the complement system. Immunol 16: 319–325.Google Scholar
  19. Day NKB, Gewurz H, Pickering RJ (1970) Ontogenetic development of Clq synthesis in the piglet. J Immunol 104: 1316–1321.PubMedGoogle Scholar
  20. Einstein LP, Schneeberger EE, Colten HR (1976) Synthesis of the second component of complement by long-term cultures of human monocytes. J Exp Med 143: 114–126.PubMedCrossRefGoogle Scholar
  21. Ezekowitz RAB, Sim RB, Hill M, Gordon S (1984) Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan. J Exp Med 159: 244–253.PubMedCrossRefGoogle Scholar
  22. Geiger H, Day NKB, Good RA (1972a) Ontogenetic development and synthesis of hemolytic C8 by piglet tissues. J Immunol 108: 1092–1096.PubMedGoogle Scholar
  23. Geiger H, Day NKB, Good RA (1972b) Ontogenetic development of the later complement components in fetal piglets. J Immunol 108: 1098–1102.PubMedGoogle Scholar
  24. 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
  25. 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
  26. Johnston RB, Alterburger KM, Atkinson AW, Curry RH (1979) Complement in the newborn infant. Pediatrics [Suppl] 64: 781–786.Google Scholar
  27. Kohler PF (1968) Quantitative comparison of complement in the mother and newborn. Fed Proc 27: 491–492.Google Scholar
  28. Mills EL, Bjorksten B, Quie PG (1979) Deficient alternative complement pathway activity in newborn sera. Pediatr Res 13: 1341–1344.PubMedCrossRefGoogle Scholar
  29. Morrison DC, Ryan JL (1979) Bacterial endotoxins and host immune response. Adv Immunol 28: 293–352.PubMedCrossRefGoogle Scholar
  30. Pangburn MK (1983) Activation of complement via the alternative pathway. Fed Proc 42: 139–144.PubMedGoogle Scholar
  31. Propp RP, Alper CA (1968) C’3 synthesis in the human fetus and lack of transplacental passage. Science 162: 672–673.PubMedCrossRefGoogle Scholar
  32. Reid KBM, Porter RR (1981) The proteolytic activation system of complement. Annu Rev Biochem 50: 433–464.PubMedCrossRefGoogle Scholar
  33. Siegel JD, McCracken GH (1981) Sepsis neonatorum. N Engl J Med 304: 642–646.PubMedCrossRefGoogle Scholar
  34. Stevenson DK, Hsu YP, McMorrow M (1980) Component concentrations and activation of the complement system in neonatal illness. A preliminary study of necrotizing enterocolitis. Eur J Pediatr 134: 255–259.PubMedCrossRefGoogle Scholar
  35. Stossel TP, Alper CA, Rosen FS (1973) Opsonic activity in the newborn: role of properdin. Pediatr 52: 134–137.Google Scholar
  36. Strunk RC, Fenton LJ, Gaines JA (1979) Alternative pathway of complement activation in full term and premature infants. Pediatr Res 13: 641–644.PubMedGoogle Scholar
  37. 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
  38. Teisberg P (1971) Genetics of the C3 system: family, mother/child, and association studies. Hum Hered 21: 458–469.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • F. Sessions Cole
    • 1
    • 2
  1. 1.The Division of Cell BiologyThe Children’s HospitalBostonUSA
  2. 2.The Joint Program in NeonatologyThe Brigham and Women’s HospitalBostonUSA

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