Granulocyte depletion and dexamethasone differentially modulate airways hyperreactivity, inflammation, mucus accumulation, and secretion induced by rmIL-13 or antigen.
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.
Singer
Monique
M
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM U485, Institut Pasteur, Paris, France.
Lefort
Jean
J
Vargaftig
B Boris
BB
D000818:Animals; D001980:Bronchi / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D001992:Bronchoalveolar Lavage Fluid; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation; D018793:Interleukin-13 / Q000096:biosynthesis*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D009195:Peroxidase / Q000096:biosynthesis; D010544:Peroxidases / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors; D014747:Vinblastine / Q000494:pharmacology
D018793:Interleukin-13; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D011994:Recombinant Proteins; D016210:Methacholine Chloride; D014747:Vinblastine; D003907:Dexamethasone; D010544:Peroxidases; D009195:Peroxidase