The reaction mechanism of human C5 in immune hemolysis.
The data presented here indicate that the C5 reaction step may proceed via the specific attachment of C5 to EAC1,4,2,3 and the formation of a hemolytically active C5 intermediate complex. During this process only a minor proportion (less than 4%) of C5 offered to EAC1,4,2,3 becomes bound, although the remaining C5 also participates in the reaction as evidenced by its inactivation in the fluid phase. Once bound, C5 is exceptionally efficient in producing hemolysis, requiring less than seven specifically bound molecules per cell for the production of a hemolytic lesion. The extent of formation of the C5 intermediate complex is primarily dependent on the number of molecules of C4, 2 and C3 present on the cells employed for its generation. In these respects, the mode of action of C5 is completely analogous to that of the other components of complement thus far investigated. The C5 step differs, however, in other aspects. The binding of C5 is influenced by C6 and C7, components which are thought to act subsequent to it in the complement sequence. In addition, the hemolytic activity of the isolated C5 intermediate complex is exceedingly labile, having an average half-life at 30 degrees C of only 9 min. This characteristic distinguishes the C5 step, along with the C2 step, as potentially rate-limiting in the complement reaction. However, unlike C2, C5 remains firmly cell-bound during the decay process and apparently undergoes an alteration in situ which renders it hemolytically unreactive. Finally, C5 is unique in that it readily adsorbs in native form to unsensitized erythrocytes. This nonspecifically bound C5 remains firmly attached, although it may be specifically utilized as a source of C5 by an ongoing complement reaction. The significance of the marked affinity of native C5 for cell-surface receptors remains to be determined.
D000327:Adsorption; D000906:Antibodies; D000936:Antigen-Antibody Complex; D000941:Antigens; D002499:Centrifugation, Density Gradient; D055598:Chemical Phenomena; D002621:Chemistry; D002859:Chromium Isotopes; D003165:Complement System Proteins / Q000032:analysis; D046508:Culture Techniques; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis; D006801:Humans; D007456:Iodine Isotopes; D011485:Protein Binding
D000906:Antibodies; D000936:Antigen-Antibody Complex; D000941:Antigens; D002859:Chromium Isotopes; D007456:Iodine Isotopes; D003165:Complement System Proteins