Activation of the alternative pathway of complement: efficient fluid-phase amplification by blockade of the regulatory complement protein beta1H through sulfated polyanions.
Current concepts of activation of the alternative pathway of complement (APC) focus on the central role of an amplification mechanism triggered by C3b which is covalently bound to the surfact of activating substances. Using sulfated polyanions as model substances, an efficient fluid-phase activation of complement is demonstrated in contrast to solid-phase activation. It is shown that particulate high-molecular weight sulfated polyanions are capable of reversible binding the guinea pig and human regulatory protein beta1H. This fixation leads to an extensive activation of C3 and factor B because the regulatory function of beta1H is blocked in the fluid-phase C3b-dependent amplification system of the APC. Addition of beta1H-depleted C4-deficient guinea pig serum reconstitutes the physiological control mechanisms of the APC. Guinea pig beta1H, purified to homogeneity, is described as a 160000 dalton protein of a single-chain structure. In addition, highly specific and sensitive test systems for beta1H are described.
D000042:Absorption; D000818:Animals; D000838:Anions; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003167:Complement Activation; D003176:Complement C3; D003179:Complement C3b / Q000276:immunology*; D003180:Complement C3b Inactivator Proteins / Q000037:antagonists & inhibitors*; D017242:Complement Factor H; D003170:Complement Pathway, Alternative; D006041:Goats; D006168:Guinea Pigs; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007700:Kinetics; D013431:Sulfates / Q000494:pharmacology*
D000838:Anions; C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D007106:Immune Sera; D013431:Sulfates; D003179:Complement C3b; D017242:Complement Factor H