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Am. J. Respir. Cell Mol. Biol., Volume 26, Number 1, January, 2002 74-84

Granulocyte Depletion and Dexamethasone Differentially Modulate Airways Hyperreactivity, Inflammation, Mucus Accumulation, and Secretion Induced by rmIL-13 or Antigen

Monique Singer, Jean Lefort, and B. Boris Vargaftig

Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM U485, Institut Pasteur, Paris, France

The intratracheal administration of interleukin (IL)-13 to hyperresponsive BP2 mice induces bronchopulmonary hyperreactivity (BHR), eosinophilia, mucus and MUC5AC accumulation, similar to those observed after ovalbumin (Ova) treatment when mice are immunized (, ). mRNAs for IL-4 peaked at 6 h after Ova challenge, then vaned, whereas IL-13 expression was stable for a longer period, suggesting different effects. Inhalation of aerosolized methacholine by immunized mice 72-96 h after Ova reduced epithelial mucus content, and enriched the bronchoalveolar lavage fluid (BALF) mucus. The role of granulocytes for mucus accumulation was studied using vinblastine or the antigranulocyte antibody RB6-8C5, which interfered to a limited extent only with allergen-induced mucus accumulation. By contrast, eosinophilic and neutrophilic inflammation, as well as BHR, were completely suppressed. Granulocytes are thus involved in Ova-induced BHR, whereas mucus accumulation and BHR are unrelated. Granulocytes seem to be more implicated in rmIL-13-induced mucus, which is reduced by the antigranulocyte antibody, whereas BHR is unaffected. The glucocorticosteroid dexamethasone reduced all the parameters evaluated after Ova or after rmIL-13. Because the effects of IL-13 are glucocorticoid-sensitive, they probably involve secondary mechanisms.

Abbreviations: Alcian Blue, AB; staining by combination of AB and then PAS, AB/PAS; bronchoalveolar lavage, BAL; BAL fluid, BALF; bronchopulmonary hyperreactivity, BHR; enzyme-linked immunosorbent assay, ELISA; eosinoperoxidase, EPO; interferon-gamma , IFN-gamma ; interleukin, IL; methacholine, Mch; myeloperoxidase, MPO; ovalbumin, Ova; Periodic Acid Schiff, PAS; porcine stomach mucins, PSM.




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