Eosinophils increase lung microvascular permeability via the peroxidase-hydrogen peroxide-halide system. Bronchoconstriction and vasoconstriction unaffected by eosinophil peroxidase inhibition.
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.
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688.
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S
Yoshikawa
S G
SG
Kayes
J C
JC
Parker
D000403:Airway Resistance / Q000502:physiology; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D016084:Bronchoconstriction / Q000502:physiology*; D002199:Capillary Permeability; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply*; D008170:Lung Compliance / Q000502:physiology; D008297:Male; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism; D014655:Vascular Resistance / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*
D013481:Superoxides; D006861:Hydrogen Peroxide; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D000640:Amitrole