Control of immune complex and zymosan-mediated anaphylatoxin generation by proteins B and H of the alternative complement pathway.
The generation of histamine releasing activity (HRA) from human basophils in fresh serum by tetanus toxoid (Te)/anti-Te complexes or by zymosan can be modulated through introduction of incremental amounts of proteins B and H of the alternative complement pathway. Serum treated at 50 degrees in order to abolish alternative pathway-mediated haemolytic activity, lost 90% of its capacity to generate HRA upon addition of Te/aTe; such loss could be reversed through additions of purified B. Amounts of B sufficient to restore normal alternative pathway haemolytic activity also restored HRA induced by Te/aTe; as little as a 33% increase above the normal serum concentration of B increased the capacity to support Te/aTe induced HRA by a factor of 1.4. In contrast, additions of incremental doses of purified H to fresh serum reduced generation of HRA by both Te/aTe and zymosan. Total inhibition was achieved by increasing the serum H concentration by 12.5-30%; further increases of H up to 200% again permitted HRA generation induced by immune complexed aTe. H also inhibited Te/aTe induced HRA in a serum heated at 50 degrees but only 30% inhibition of HRA could be achieved over a range of H inputs up to 187% above normal serum concentration. Additions of H also inhibited HRA generation in fresh serum when induced with plain or C3b-coated zymosan (Z) particles. By increasing the serum concentration of H from 12.5 to 125%, dose-dependent inhibition of HRA generation was observed; the H input necessary to suppress 48% of HRA generation was ten times higher when HRA was generated by Z-C3b than by plain zymosan. Thus, the complement-dependent generation of HRA from fresh serum strongly depends on modest variations in the concentrations of the two regulatory proteins B and H of the alternative complement pathway, suggesting their direct effect on generation of anaphylatoxins C3a and C5a.
D000706:Anaphylatoxins / Q000096:biosynthesis*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D003167:Complement Activation; D003179:Complement C3b / Q000276:immunology; D003180:Complement C3b Inactivator Proteins / Q000276:immunology*; D011415:Complement Factor B / Q000276:immunology*; D017242:Complement Factor H; D003170:Complement Pathway, Alternative; D004792:Enzyme Precursors / Q000276:immunology*; D006636:Histamine Release; D006801:Humans; D066298:In Vitro Techniques; D010452:Peptide Biosynthesis; D013745:Tetanus Toxoid / Q000276:immunology; D015054:Zymosan / Q000494:pharmacology*
D000706:Anaphylatoxins; D000936:Antigen-Antibody Complex; C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D004792:Enzyme Precursors; D013745:Tetanus Toxoid; D003179:Complement C3b; D017242:Complement Factor H; D015054:Zymosan; D011415:Complement Factor B