Measurement of C3 Fragment Deposition on Cells
Measurement of complement-mediated cytolysis, described in Chapter 5, is the index most frequently used for assessing aspects of complement activation or regulation. However, other consequences of complement activation are probably of more relevance in vivo. Complement plays a major role in enhancing the generation of specific antibodies and provides an interface between the humoral and cellular immune responses (1, 2, 3, 4). Complement also increases the binding of phagocytes to target cells by opsonizing the complement activating surface and generates chemoattractants and anaphylatoxins to recruit nearby phagocytes (5,6). Through these mechanisms, complement not only provides a first line defence against invading pathogens but also acts as the glue that holds the major components of the immune system together. These opsonic, chemoattractant, and anaphylactic activities are largely properties of C3 (and C5) activation fragments. Furthermore, large amounts of C3 fragments can be deposited on the surface of cells without causing significant amounts of lysis. Measurement of C3-deposition is therefore a more sensitive and probably more relevant indicator of complement activation than measurement of cytolysis.
KeywordsComplement Activation Membrane Cofactor Protein Complement Attack Cytolysis Assay Terminal Complement Component
- 3.Thornton B. P., Vetvicka V., and Ross G. D. (1996) Function of C3 in ahumoral response: iC3b/C3dg bound to an immune complex generated with natural antibody and a primary antigen promotes antigen uptake and the expression of co-stimulatory molecules by all B cells, but only stimulates immunoglobulin synthesis by antigen-specific B cells. Clin. Exp. Immunol. 104, 531–537.PubMedCrossRefGoogle Scholar
- 4.Brahmi Z., Csipo I., Bochan M. R., Su B., Montel A. H., and Morse P. A., Jr. (1995) Synergistic inhibition of human cell-mediated cytotoxicity by complement component antisera indicates that target cell lysis may result from an enzymatic cascade involving granzymes and perforin. Nat. Immun. 14, 271–285.PubMedGoogle Scholar
- 8.Kemp P. A., Spragg J. H., Brown J. C., Morgan B. P., Gunn C. A., and Taylor P. W. (1992) Immunohistochemical determination of complement activation in joint tissues of patients with rheumatoid arthritis and osteoarthritis using neoantigen-specific monoclonal antibodies. J. Clin. Lab. Immunol. 37, 147–162.PubMedGoogle Scholar
- 10.Aguado M. T., Lambris J. D., Tsokos G. C., Burger R., Bitter-Suermann D., Tamerius J. D., et al. (1985) Monoclonal antibodies against complement 3 neoantigens for detection of immune complexes and complement activation. Relationship between immune complex levels, state of complex levels, state of C3, and numbers of receptors for C3b. J. Clin. Invest. 76, 1418–1426.PubMedCrossRefGoogle Scholar