Trinitrophenylated red cells (E-TNP) as a model for antibody-independent activation of the complement system via the classical pathway.
Recently, it was shown that DNP-substituted human serum albumin (DNP-HSA) bound directly C1q, a subcomponent of C1. Evidence is presented that TNP-conjugated erythrocyte (E-TNP) were lysed by autologous sera as source of complement (C). The lysis was strongly dependent on the TNP substitution rate so that the TNP-carrying erythrocytes can be used directly as an indicator for the TNP-C interaction. The TNP-induced lysis of erythrocytes required the presence of C1q, C4, and Ca++, indicating a dependency on the classical pathway of C. Purified C1 is directly bound to E-TNP; C1 bound to E-TNP could be transferred to EAC4. From E-TNP-C1 the intermediates E-TNP-C14 and E-TNP-C142 can be formed by successive addition of C4 and C2 similarly to EAC14 and EAC142. Native C1 can be activated to C1 by E-TNP in the same fashion as by EA. The E-TNP model provides evidence that the "activated" Fc part of the antibody molecule is not unique in its ability to trigger the internal activation of C1. Molecules with negatively charged groups, like polyanions, or molecules with high electron dense groups, like DNP or TNP, can activate the C system via the classical pathway by binding directly to C1q.
D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D003172:Complement C1 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D004912:Erythrocytes / Q000276:immunology*; D006461:Hemolysis; D006801:Humans; D009578:Nitrobenzenes / Q000276:immunology*; D012756:Sheep; D014301:Trinitrobenzenes / Q000276:immunology*
D003172:Complement C1; D003181:Complement C4; D009578:Nitrobenzenes; D014301:Trinitrobenzenes; D003165:Complement System Proteins; D002118:Calcium