Inflammatory Mediators Involved in Antigen-induced Airway Microvascular Leakage in Guinea Pigs

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Abstract
Antigen challenge of ovalbumin (OA)-sensitized guinea pigs results in significant (p < 0.05) increases in vascular permeability to Evans blue (EB) dye in the airways, esophagus, and bladder. Mean values .+-. SEM in ng EB/mg wet weight tissue for unsensitized versus sensitized animals were: trachea, 23.6 .+-. 6.6 versus 92.5 .+-. 11.1; main bronchi, 31.1 .+-. 12.2 versus 153.1 .+-. 14.9; "central" intrapulmonary airways (ipa), 34.6 .+-. 11.2 versus 101.3 .+-. 6.2; and "peripheral" ipa, 26.2 .+-. 6.8 versus 93.5 .+-. 13.6. We investigated the involvement of several mediators of inflammation in this process. FPL 55712, a sulfidopeptide leukotriene receptor antagonist, caused significant inhibition of leakage in trachea (to 55.1 .+-. 9.8) and main bronchi (91.7 .+-. 15.8). Blockade of the cyclooxygenase and lipoxygenase pathways with BW 755C, but not of the cyclooxygenase pathway alone with indomethacin, also significantly reduced EB dye extravasation in trachea (55.1 .+-. 18.0), main bronchi (71.7 .+-. 23.0), and "central" ipa (62.7 .+-. 16.4). The histamine antagonists, chloropheniramine and cimetidine, only inhibited microvascular leakage in main bronchi (94.4 .+-. 20.0). PAF-receptor blockade with the ginkgolide mixture BN 52063 had no effect. Nedocromil sodium, a mast cell stabilizer and an inhibitor of inflammatory cell activation, caused significant inhibition throughout the airways; trachea, 50.4 .+-. 10.6; main bronchi, 72.0 .+-. 15.3; "central" ipa 61.0 .+-. 8.6; "peripheral" ipa 41.9 .+-. 12.2. Thus, histamine and lipoxygenase products (in particular, leukotrienes), but not PAF, may mediate the antigen-induced increase in vascular permeability to different degrees in differing regions of the respiratory tract in guinea pigs.

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