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

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, chlorpheniramine 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.