Ultrastructural evidence for extravascular platelet recruitment in the lung upon intravenous injection of platelet-activating factor (PAF-acether) to guinea-pigs.
Bronchoconstriction and degenerative lesions of the bronchial epithelium were observed microscopically 1 min after the i.v. injection of 100 ng/kg of platelet-activating factor (PAF-acether) to the anaesthesized guinea-pig. Constricted arterioles containing marginated polymorphonuclear neutrophils and platelet aggregates were seen, as well as alveolar capillaries obstructed by thrombi formed by partially or totally degranulated platelets. Three minutes after the injection of PAF-acether, platelet diapedesis to the alveolar septa and lumen was clearly observed. Bronchoconstriction was still present at 3 min, but subsided after 60 min, whereas oedema of the submucosa persisted accompanied by an infiltration of eosinophils and neutrophils. The infusion of prostacyclin prevented the formation of platelet aggregates and platelet diapedesis due to PAF-acether, but the morphological evidence of bronchial constriction was not modified. Aspirin failed completely to modify the effects of PAF-acether. Our results show that PAF-acether causes early formation and deposition of platelet aggregates, accompanied by the margination of polymorphonuclear neutrophil leucocytes in pulmonary vessels of the guinea-pig. Since bronchoconstriction persisted when platelet aggregation was inhibited with prostacyclin, aggregation by itself would not account for this effect. Early platelet diapedesis in the vicinity of bronchial smooth muscle corroborates previous evidence that platelets contain and release bronchoconstrictor substances, which operate by cyclo-oxygenase-independent mechanisms and are possibly involved with the physiopathology of lung inflammation during immediate hypersensitivity.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D001980:Bronchi / Q000276:immunology / Q000648:ultrastructure; D003251:Constriction, Pathologic; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D008168:Lung / Q000648:ultrastructure*; D008854:Microscopy, Electron; D009504:Neutrophils / Q000648:ultrastructure; D010972:Platelet Activating Factor / Q000276:immunology*; D010974:Platelet Aggregation / Q000187:drug effects; D013997:Time Factors
D010972:Platelet Activating Factor; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D001241:Aspirin