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Comparison of the eosinophilotactic effect of PAF-acether and antigen in vivo: role of PAF-acther antagonist and platelets
PROSTAGLANDINS
COMPARISON OF THE EOSINOPHILOTACTIC EFFECT OF PAF-ACETHER AND ANTIGEN I/V V/V0 : ROLE OF PAF-ACETHER ANTAGONISTS AND PLATELETS A. Lellouch-Tubiana*, J. Lefortl, M.-T. Simon*, A. Pfister*, C. Da Lage* and B. B. Vargaftig’ Unite des Venins-Unite Associbe lnstitut Pasteur INSERM no 285, 25, rue du Dr Roux, 75015 Paris (France) * Laboratoire d’Histologie, Faculte de Mhdecine Necker-Enfants Malades, 156, rue de Vaugirard, 75015 Paris (France) l
I.v. administration of PAF-acether to the guinea-pig induces bronchoconstriction, hypotension, intravascular platelet aggregation, endothelial disruption and platelet and neutrophil diapedesis. These effects are followed within 1 hour by an eosinophilic infiltration in the bronchial wall. Bronchoconstriction and eosinophil infiltration are two major features of asthma. Selective bronchial eosinophilia characterizes especially late asthmatic reactions. Neverthless, no histological studies relating PAF-acether administration to late cellular changes were reported until now. This led us to study the effects of PAF-acether six and twenty-four hours after its i.v. injection and to compare them with those of experimental passive anaphylactic shock, used as a model for asthma. Our study shows a striking lung eosinophil infiltration, six hours after PAF-acether or antigen (ovalbumin) iv. administration, particulary in the bronchial walls. Bronchial mucous plugs containing eosinophils were noted in the bronchial lumen. Epithelial damage was followed after twenty-fous hours by mucous metaplasia of the bronchial epithelium. All these histological findings, which stongly suggest the pathological features of late-phase reactions of human asthma, were never reported after PAF-acether. The latter may thus play an important role in the eosinophil recruiment to the site of allergic reactions. It has also been shown that PAF-acether is the most potent eosinophilotactic agent known. Some authors suggested that the eosinophil is a prime mediator of the pathophysiology of bronchial asthma and releases proteins toxic for the respiratory epithelium. Mepyramine is a specific anti-histamine which protects guinea-pigs from anaphylactic bronchoconstriction. Even though bronchoconstriction was indeed abrogated in mepyramine-treated animals, all morphological evidences of shock, as described above, were present. Similarly, pre-treatment with the selective leukotriene antagonist FPL 55712 and with the cyclooxygenase inhibitor aspirin, failed to prevent the described ulstrastructural alterations. In contrast, two PAF-acether antagonists (BN 52021 and WEB 2086) injected i.v. 5 minutes before PAF-acether, greatly prevented the eosinophil infiltration six hours later. When the same antagonists were administered to antigen-injected guinea-pigs, the number of infiltrated eosinophils was also markedly reduced. In the same way, when PAF-acether and/or ovalbumin were injected to guinea-pigs after anti-platelet serum and/or prostacyclin, the eosinophil infiltration was significantly reduced, suggesting that platelets are important for the subsequent PAF-acether- induced eosinophil infiltration. Our results support an essential role for PAF-acether and for platelets in an experimental model of asthma.
,168
AUGUST
1987 VOL. 34 NO. 2
COMPARISON OF THE EOSINOPHILOTACTIC EFFECT OF PAF-ACETHER AND ANTIGEN I/V V/V0 : ROLE OF PAF-ACETHER ANTAGONISTS AND PLATELETS A. Lellouch-Tubiana*, J. Lefortl, M.-T. Simon*, A. Pfister*, C. Da Lage* and B. B. Vargaftig’ Unite des Venins-Unite Associbe lnstitut Pasteur INSERM no 285, 25, rue du Dr Roux, 75015 Paris (France) * Laboratoire d’Histologie, Faculte de Mhdecine Necker-Enfants Malades, 156, rue de Vaugirard, 75015 Paris (France) l
I.v. administration of PAF-acether to the guinea-pig induces bronchoconstriction, hypotension, intravascular platelet aggregation, endothelial disruption and platelet and neutrophil diapedesis. These effects are followed within 1 hour by an eosinophilic infiltration in the bronchial wall. Bronchoconstriction and eosinophil infiltration are two major features of asthma. Selective bronchial eosinophilia characterizes especially late asthmatic reactions. Neverthless, no histological studies relating PAF-acether administration to late cellular changes were reported until now. This led us to study the effects of PAF-acether six and twenty-four hours after its i.v. injection and to compare them with those of experimental passive anaphylactic shock, used as a model for asthma. Our study shows a striking lung eosinophil infiltration, six hours after PAF-acether or antigen (ovalbumin) iv. administration, particulary in the bronchial walls. Bronchial mucous plugs containing eosinophils were noted in the bronchial lumen. Epithelial damage was followed after twenty-fous hours by mucous metaplasia of the bronchial epithelium. All these histological findings, which stongly suggest the pathological features of late-phase reactions of human asthma, were never reported after PAF-acether. The latter may thus play an important role in the eosinophil recruiment to the site of allergic reactions. It has also been shown that PAF-acether is the most potent eosinophilotactic agent known. Some authors suggested that the eosinophil is a prime mediator of the pathophysiology of bronchial asthma and releases proteins toxic for the respiratory epithelium. Mepyramine is a specific anti-histamine which protects guinea-pigs from anaphylactic bronchoconstriction. Even though bronchoconstriction was indeed abrogated in mepyramine-treated animals, all morphological evidences of shock, as described above, were present. Similarly, pre-treatment with the selective leukotriene antagonist FPL 55712 and with the cyclooxygenase inhibitor aspirin, failed to prevent the described ulstrastructural alterations. In contrast, two PAF-acether antagonists (BN 52021 and WEB 2086) injected i.v. 5 minutes before PAF-acether, greatly prevented the eosinophil infiltration six hours later. When the same antagonists were administered to antigen-injected guinea-pigs, the number of infiltrated eosinophils was also markedly reduced. In the same way, when PAF-acether and/or ovalbumin were injected to guinea-pigs after anti-platelet serum and/or prostacyclin, the eosinophil infiltration was significantly reduced, suggesting that platelets are important for the subsequent PAF-acether- induced eosinophil infiltration. Our results support an essential role for PAF-acether and for platelets in an experimental model of asthma.
,168
AUGUST
1987 VOL. 34 NO. 2