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

Abstract

Antigen challenge of ovalbumin (OA)-sensitized guinea pigs results in significant (p less than 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.

Perivascular Mast Cells Promote Atherogenesis and Induce Plaque Destabilization in Apolipoprotein E–Deficient Mice

“…31,32 We indeed observed that after intradermal injection of 5ϫ10 5 activated MC/9 cells in mice, vascular leakage as judged by Evans Blue spot size was significantly enhanced compared with PBS and was demonstrated to only be inhibited by the H 1 -receptor antagonist triprolidine (online-only Data Supplement Figure VII, PϽ0.001). More importantly, carotid artery lesions, perivascularly challenged with DNP and injected with Rhodamine 6G to label circulating leukocytes, contained a higher number of Rhodamine-positive cells than controls (Pϭ0.0002) ( Figure 7A) at 3 days after challenge.…”

Rupatadine: pharmacological profile and its use in the treatment of allergic rhinitis

“…Role of platelet-activating factor in allergic rhinitis Platelet-activating factor (PAF) is an important mediator of AR, as concluded from the effectiveness of the PAF antagonist ABT-491 in rat and guinea-pig models of AR [10,11]. The biological properties of this mediator include vasodilation and an increase in vascular permeability that may contribute to the appearance of rhinorrhoea and nasal congestion [12,13]. Both PAF and its metabolite, lyso-PAF, have been detected in the nasal fluids and plasma of patients with rhinitis [14,15].…”

Two Pharmacological Phases in Antigen-Induced Immediate Airway Response in Rats

“…3,4) On the other hand, since pharmaceutical targets for new asthmatic drugs have become more immunologically diverse and specific, detailed immunological analysis of mechanisms in animal models is required to determine with precision the efficacies of new drug candidates. However, the guinea pig airway model is not sufficient for this purpose, since immunological and genetic research on guinea pigs has not been performed in detail.…”