The characteristics of the plasma factors required for passive platelet damage induced by an antigen-antibody system in which the antigen is not an integral part of the platelet have been studied in an in vitro system consisting of a standardized suspension of washed rabbit platelets, autologous plasma, rabbit anti-protein antibody and the corresponding antigen. The release of histamine served as an indication of platelet damage. Pseudo- and euglobulin fractions of rabbit plasma prepared by dialysis against distilled water at acid pH are unable to support the platelet-damaging reaction alone, but the activity is restored when the fractions are combined. Treatment of the plasma with zymosan and NH4OH abolishes activity, as does the presence of salicylaldoxime in the reaction mixture. When incubated with whole rabbit plasma at 0°C for 10 min, a preformed immune precipitate acquires an enhanced ability to release histamine from platelets in the presence of additional plasma, in comparison with the same amount of an untreated precipitate. The uptake of this enhancing activity is blocked by the presence of EDTA, and a guinea pig antibody prepared against such a treated precipitate inhibits both histamine release from platelets and immune hemolysis by rabbit complement. It is suggested that these findings are entirely consistent with the known behavior of hemolytic complement and would be compatible with the participation of the complement system in passive damage of platelets by an unrelated antigen-antibody reaction.

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