Intratracheal E. coli lipopolysaccharide induces platelet-dependent bronchial hyperreactivity.
Bronchial hyperresponsiveness (BHR) characterizes asthma and accompanies respiratory infections. Because endotoxin [lipopolysaccharide (LPS)] induces either hyper- or hyporesponsiveness of the guinea pig airways and protects against bronchopulmonary anaphylaxis in sensitized guinea pigs, we compared the effects of the intratracheal administration of Escherichia coli LPS on bronchopulmonary responsiveness to intravenous serotonin or acetylcholine in sensitized and nonsensitized guinea pigs. LPS (1 mg) induced BHR within 1-2 h, with a threefold increase in the bronchial response after serotonin challenge in both groups (n = 6; P < 0.005) and a marked influx of neutrophils into the perivascular and peribronchial connective tissue and the bronchoalveolar lavage fluid. This BHR was not leukocyte dependent, since it was still observed in animals depleted of circulating leukocytes with vinblastine and was not modified by antineutrophil serum, unless platelet counts were < 100,000/mm3. This suggested that LPS-induced BHR involves platelets, and indeed antiplatelet serum, which depleted platelets, or prostacyclin, which inhibited platelets, was effective in suppressing BHR. Neither aspirin, mepyramine, nor the platelet-activating factor antagonist WEB 2170, administered before LPS instillation, prevented BHR, whereas the association of methysergide, mepyramine, and aspirin was effective, without modifying platelet and leukocyte counts. This association has been shown to prevent the release of ATP by ex vivo platelets. Our results suggest that platelets or a platelet-derived product mediates LPS-induced BHR.
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-Institut National de la Santé et de la Recherche Médicale Unité no. 285, Paris, France.
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Vincent
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Lefort
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Bureau
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Vargaftig
D000109:Acetylcholine / Q000494:pharmacology; D000418:Albumins / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism; D001792:Blood Platelets / Q000276:immunology / Q000502:physiology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002199:Capillary Permeability / Q000502:physiology; D004912:Erythrocytes / Q000502:physiology; D004926:Escherichia coli; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010976:Platelet Count; D012701:Serotonin / Q000494:pharmacology; D013670:Sodium Pertechnetate Tc 99m; D014747:Vinblastine / Q000494:pharmacology
D000418:Albumins; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D012701:Serotonin; D014747:Vinblastine; D013670:Sodium Pertechnetate Tc 99m; D000109:Acetylcholine