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Eosinophils have been implicated as effector cells in producing vascular and bronchial constriction and increased microvascular permeability in the lung. Hypohalous acids produced by the eosinophil peroxidase (EPO)-hydrogen peroxide (H2O2)-halide system are stable cytotoxic oxidants. We measured the effects of EPO inhibition in activated eosinophils on vascular permeability, assessed using the capillary filtration coefficient (Kf,c), vascular resistance (Rt,vasc), and airway resistance (Raw) in isolated rat lungs perfused with 5% bovine albumin in Kreb's solution. Eosinophils were harvested by bronchoalveolar lavage of Toxicara canis-infected rats. Infusion of 2 x 10(6) phorbol myristate acetate (PMA)-activated cells produced a 3.3-fold increase in Rt,vasc at 30 min, primarily caused by small vessel constriction, a 2.5-fold increase in Raw at 150 min, and a 1.8-fold increase in Kf,c at 90 min. Inhibition of EPO using 3-amino-1,2,4-triazole (3-AT) prevented the increases in Kf,c, but not those in eosinophil superoxide production, Rt,vasc, or Raw. Addition of 2 mM sodium bromide as preferential EPO substrate caused Kf,c, but not Rt,vasc, or Raw, to increase significantly (2.5-fold) compared with activated eosinophils alone. Thus, the acute changes in microvascular permeability were modulated by activity of the EPO-H2O2-Halide system, but the increased vascular and bronchial resistances were mediated through a different pathway.

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The effects of eosinophils activated with phorbol myristate acetate (PMA) on isolated perfused rat lungs were examined. Eosinophils were obtained from lungs of rats infected with Toxocara canis by bronchoalveolar lavage, incubated with PMA, and administered to an isolated perfused rat lung preparation. Vascular endothelial permeability was assessed by measuring the capillary filtration coefficient (Kf,c) in the perfused lungs. In lungs receiving either no eosinophils (control) or nonactivated eosinophils, there were no changes in pulmonary hemodynamics or Kf,c. However, in lungs receiving 2 x 10(6) eosinophils activated with PMA, there was a transient 4.8-fold increase in pulmonary vascular resistance that peaked at 30 min, primarily due to the constriction of small arteries and veins. After the initial pressor response, Kf,c was increased to 7.5 times control at 130 min and resulted in marked lung edema, increased wet-dry weight ratios, and edema on histologic examination. Pulmonary arterial pressure and Kf,c responses were dose related for eosinophil numbers between 1 x 10(6) and 4 x 10(6) cells. Peak airway pressure (Paw) during constant tidal volume ventilation also increased in lungs receiving activated eosinophils compared to the control and nonactivated eosinophil groups. These findings indicate that activated eosinophils are potent effector cells and can cause pulmonary vasoconstriction, bronchoconstriction, and vascular endothelial injury without widespread plugging of capillaries by aggregated eosinophils.