Regulation of the activity of platelet-bound C3 convertase of the alternative pathway of complement by platelet factor H.
The alternative pathway of complement is regulated on the surface of homologous blood cells at the C3 amplification step by the membrane protein decay-accelerating factor, as well as by the plasma protein factor H. We have reported elsewhere that platelets from patients with paroxysmal nocturnal hemoglobinuria regulate the activity of the C3 convertase C3bBb, even though they lack decay-accelerating factor. We now report that normal human platelets contain factor H, which was released from the platelet in response to complement deposition or thrombin stimulation. Factor H was localized to the platelet alpha granules by immunocytochemical techniques. As determined by a solid-phase radioimmunoassay, thrombin-stimulated platelets released approximately equal to 54 ng of factor H per 10(8) platelets. The release of factor H in response to complement or thrombin was inhibited by treating the platelets with metabolic inhibitors. Such inhibition resulted in a 3-fold increase in the activity of C3bBb. Platelets that released factor H bound only half as many molecules of radiolabeled factor B to platelet-bound C3b than platelets that could not release factor H. Treatment of platelets with anti-decay-accelerating factor antibody had no effect on the activity of C3bBb unless the release of factor H was blocked. Therefore, so far as we know, human platelets have a unique mechanism for the regulation of the alternative pathway of complement.
D003166:Complement Activating Enzymes / Q000097:blood*; D003167:Complement Activation; D003176:Complement C3 / Q000494:pharmacology; D050577:Complement C3-C5 Convertases / Q000097:blood*; D003180:Complement C3b Inactivator Proteins / Q000502:physiology*; D017242:Complement Factor H; D003170:Complement Pathway, Alternative; D005470:Fluorometry; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000201:enzymology; D006801:Humans; D008854:Microscopy, Electron
C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases