An ultrastructural study of the mechanisms of platelet-endotoxin interaction.
Electron microscopy has confirmed previous studies and has provided much new information on the mechanism of endotoxin-platelet interaction. The Boivin lipopolysaccharide preparation is particulate, and on electron microscope examination appears as a three-layered structure, morphologically similar to bacterial cell wall. In vitro and in vivo experiments have demonstrated that these endotoxin particles adhere to platelets. In some species, particularly the rabbit, this is associated with loss of platelet contents, due to lysosomal and cell membrane lysis, resulting in platelet sphering and apparent cell death. Serial observation of degranulating platelets and metabolic studies indicate that although some platelet engulfment of endotoxin occurs, degranulation is not dependent upon phagocytosis. Several observations suggest that these endotoxin effects are mediated through immune mechanisms: (1) Inactivation of complement in the suspending plasma by heating to 56 degrees C, anticoagulation with EDTA, a reaction temperature of 5 degrees C, ammonium hydroxide incubation, and adsorption with either zymosan or washed antigen-antibody complexes, inhibits both endotoxin adherence and platelet degranulation. (2) The reaction requires a plasma cofactor, possibly antibody, which can be adsorbed out by endotoxin. (3) Endotoxin adheres selectively to nonprimate platelets and primate red cells, a pattern conforming to immune adherence, a phenomenon requiring antigen, antibody, and complement. It is suggested that endotoxin-induced platelet damage is dependent upon the intimate contact provided by immune adherence. We have not established whether degranulation is an endotoxin or complement effect. The species variation in susceptibility to endotoxin also merits further investigation.
D000818:Animals; D000937:Antigen-Antibody Reactions; D000963:Antimetabolites / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D003165:Complement System Proteins; D004285:Dogs; D004492:Edetic Acid; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D007118:Immunoassay; D066298:In Vitro Techniques; D008297:Male; D010587:Phagocytosis; D011817:Rabbits; D051381:Rats
D000963:Antimetabolites; D004731:Endotoxins; D003165:Complement System Proteins; D004492:Edetic Acid