Characterization of alternative pathway inhibition by a serum derived, low molecular weight complement inhibitor

Autor: P J, Baker, C J, Parker, S G, Osofsky
Rok vydání: 1984
Předmět:
Zdroj: Clinical and experimental immunology. 55(1)
ISSN: 0009-9104
Popis: Normal human serum contains an inhibitor of complement which is distinguished by its small size of 500 daltons, the low molecular weight inhibitor (LMWI). When LMWI was present during incubation of zymosan or cobra venom factor with serum, formation of complement reactive complexes was blocked as measured by failure of these mixtures to lyse susceptible erythrocytes from patients with paroxysmal nocturnal haemoglobinuria (PNH). Addition of LMWI to pre-formed complexes had no effect on their subsequent haemolytic activity. When dialysis was used to remove LMWI from reaction mixtures, it was shown that LMWI had not irreversibly altered any of the complement components. Purified components were used to demonstrate that LMWI prevented factor D activation of cobra venom factor-factor B complexes. LMWI also strongly inhibited binding of 125I-factor B to human erythrocytes bearing C3b and had little or nor effect on binding of 125I-factor H to the C3b bearing cells. Factor B binding to C3b was equally inhibited on normal and PNH erythrocytes. Thus, a dialysable fraction from normal human serum prevents activation of human complement by blocking formation, but not the activity of the C3/C5 convertase. These low molecular weight inhibitors result in inhibition of factor B binding to C3b and inhibition of factor D activation of C3bB complexes.
Databáze: OpenAIRE