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Bronchoconstriction and eosinophil recruitment in guinea pig lungs after platelet activating factor administration
Abstract:
Using a forced expiratory maneuver to measure flow volume loops, we evaluated the ability of platelet activating factor (PAF) to induce acute bronchospasm and in histological changes associated with bronchial asthma in guinea pigs. We determined both the dose-response curve and the time course of PAF-induced bronchoconstriction. Eight guinea pigs with weights ranging from 350 to 450 g were anesthetized, tracheotomized, and then paralyzed with gallamine. Baseline pulmonary function tests (PFT) were done. Different doses (25, 50, 100, 200, and 500 ng/kg) of PAF were injected through the jugular vein, and serial PFTs were done at 30 sec, 2, 5, and 20 min after each dose of PAF. Acetylcholine provocation testing was done following the 200 ng/kg dose of PAF. The PFTs included a forced expiratory maneuver, airway opening pressure (PaO), and total lung compliance (TLC). After all PFTs were completed, cell counts were done on fluid obtained from bronchoalveolar lavage (BAL) and the lungs were removed for histological study. Eight other guinea pigs were used as controls. The results showed that with increasing doses of PAF from 25 ng/kg to 200 ng/kg, all lung function parameters, including vital capacity, peak flow, MFEF 75%, MFEF 50%, MFEF 25%, and total lung compliance, gradually decreased. However, a further increase of the dose of PAF up to 500 ng/kg did not result in continued worsening of PFTs. The most severe bronchoconstriction occurred 30 sec after PAF was injected, and it gradually resolved thereafter. PAF injection also induced a severe inflammatory reaction of the airway and lung tissue, characterized by congestion, edema, inflammatory cell (especially lymphocytes and eosinophils) infiltration, and desquamation of bronchial epithelial cells. In conclusion, in the guinea pig model, PAF can induce acute reversible bronchospasm and bronchial hyperreactivity, as well as the typical histological changes of bronchial asthma.