Leukotrienes, IL-13, and chemokines cooperate to induce BHR and mucus in allergic mouse lungs.
In mice, intratracheal challenges with antigen (ovalbumin) or recombinant murine interleukin-13 (IL-13) induce lung inflammation, bronchial hyperreactivity (BHR), and mucus accumulation as independent events (Singer M, Lefort J, and Vargaftig BB. Am J Respir Cell Mol Biol 26: 74-84, 2002), largely mediated by leukotrienes (LT). We previously showed that LTC(4) was released 15 min after ovalbumin, and we show that it induces the expression of monocyte chemoattractant proteins 1 and 5 and KC in the lungs, as well as IL-13 mRNA. Instilled intratracheally, these chemokines induced BHR and mucus accumulation, which were inhibited by the 5-lipoxygenase inhibitor zileuton and by the cysteinyl-LT receptor antagonist MK-571, suggesting mediation by cysteinyl-LT. Because these chemokines also induced release of LT into the bronchoalveolar lavage fluid and IL-13 into the lungs, we hypothesize that LT- and chemokine-based loops for positive-feedback regulations cooperate to maintain and amplify BHR and lung mucus accumulation after allergic challenge and in situations where IL-13, LT, or chemokines are generated.
Vargaftig
B Boris
BB
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-Institut National de la Santé et de la Recherche Médicale U485, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France.
Singer
Monique
M
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018925:Chemokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006967:Hypersensitivity / Q000150:complications* / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017997:Leukotriene C4 / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D008679:Metaplasia; D051379:Mice; D008815:Mice, Inbred Strains; D009077:Mucins / Q000235:genetics; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology
D018925:Chemokines; D018793:Interleukin-13; D015289:Leukotrienes; D009077:Mucins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D017997:Leukotriene C4; D010047:Ovalbumin