Participation of platelets in the physiologic alterations of the AGEPC response and of IgE anaphylaxis in the rabbit. Effects of PGI2 inhibition of platelet function.
To further clarify the platelet dependence of acetyl glyceryl ether phosphorylcholine (AGEPC) physiologic activity and of IgE anaphylaxis in the rabbit, PGI2 was employed as an inhibitor of in vivo platelet function. Intravenous infusion of PGI2 (1 to 2 micrograms/kg/min) inhibited the AGEPC-induced decrease in dynamic compliance, increase in total pulmonary resistance, and transient decrease in tidal volume, but the right ventricular hypertension, bradycardia, and apnea were unaffected. Although PGI2 itself produced a marked systemic hypotension, AGEPC still induced a bimodal hypotensive response. Documentation that platelet function was inhibited by PGI2 included partial inhibition of AGEPC-induced thrombocytopenia, abrogation of platelet secretion (as assessed by plasma platelet factor 4 levels), and inhibition of ex vivo platelet aggregation. The AGEPC-induced leukopenia was not affected. In another group of rabbits, chlorpheniramine pretreatment inhibited the lung mechanical changes induced by AGEPC but did not affect the ventilatory or circulatory alterations, indicating that the lung mechanical alterations (but not any of the other alterations) are mediated by platelet-secreted histamine acting via H1 receptors. In IgE-producing rabbits intravenously challenged with antigen, PGI2 had no effect on any of the physiologic alterations, despite substantial inhibition of platelet secretion. From these results, together with previous platelet depletion studies, we conclude that AGEPC may be a significant mediator of the circulatory alterations and apnea of rabbit IgE anaphylaxis by platelet-independent mechanisms, but neither AGEPC nor platelets appear to be important in mediating the anaphylactic lung mechanical alterations.
D000707:Anaphylaxis / Q000097:blood* / Q000139:chemically induced / Q000503:physiopathology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001792:Blood Platelets / Q000502:physiology*; D002744:Chlorpheniramine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology / Q000502:physiology; D005260:Female; D007073:Immunoglobulin E; D008297:Male; D010972:Platelet Activating Factor / Q000502:physiology*; D011817:Rabbits
D000941:Antigens; D010972:Platelet Activating Factor; D007073:Immunoglobulin E; D002744:Chlorpheniramine; D011464:Epoprostenol