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Am. J. Respir. Cell Mol. Biol., Volume 26, Number 5, May, 2002 579-586

Characterization of Lung Hyperresponsiveness, Inflammation, and Alveolar Macrophage Mediator Production in Allergy Resistant and Susceptible Rats

Eric Careau, Jocelyne Sirois, and Elyse Y. Bissonnette

Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Québec, Canada

To better understand asthma pathogenesis, we characterized airway responsiveness, lung inflammation, and mediator production of alveolar macrophages (AM) after allergen sensitization and challenge in two strains of rats showing different susceptibilities in developing airway allergic reactions. Airway responsiveness to acethylcholine was measured 24 h after ovalbumin (OVA) challenge, whereas bronchoalveolar lavages were performed 5 min, 8 h, and 24 h after challenge. Brown Norway rats showed airway hyperresponsiveness after challenge, whereas lung resistance remained unchanged in Sprague-Dawley rats. Interestingly, Sprague-Dawley rats developed a neutrophilic inflammation, whereas both neutrophils and eosinophils were increased in Brown Norway rats. AM mediator production varied with time with a lower tumor necrosis factor (TNF) and interleukin (IL)-10 release at 8 h after challenge. OVA challenge stimulated spontaneous TNF and IL-10 release by AM isolated 24 h after challenge in both strains of rats, although AM from Brown Norway rats released significantly more IL-10 and TNF. Furthermore, nitric oxide production was increased only in OVA-challenged (24 h) Brown Norway rats. Our results suggest that AM may participate to the expansion of Th2 inflammation in Brown Norway rats and that differences in AM mediator production may explain, in part, distinct allergic susceptibilities in these two strains of rats.

Abbreviations: acetylcholine, ACh; alveolar macrophages, AM; bronchoalveolar lavage, BAL; interferon-gamma , IFN-gamma ; immunoglobulin, Ig; interleukin, IL; macrophage inflammatory protein, MIP; nitric oxide, NO; ovalbumin, OVA; phosphate-buffered saline, PBS; pulmonary resistance, RL; T helper, Th; tumor necrosis factor, TNF.




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