Published ahead of print on May 18, 2005, doi:10.1165/rcmb.2004-0213OC
© 2005 American Thoracic Society DOI: 10.1165/rcmb.2004-0213OC Interleukin-17 as a Recruitment and Survival Factor for Airway Macrophages in Allergic Airway InflammationThe Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden; and The Unit for Lung Investigations, National Institute for Health Development, Tallinn, Estonia Correspondence and requests for reprints should be addressed to Svetlana Sergejeva, M.D., Ph.D., The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden. Current address: Puuvilla 19A-5, 10314 Tallinn, Estonia. E-mail: Svetlana.Sergejeva{at}lungall.gu.se Recent data indicate that the proinflammatory cytokine, interleukin (IL)-17, stimulates certain effector functions of human macrophages. We evaluated whether IL-17 mediates allergen-induced accumulation of airway macrophages and, if so, whether such an effect relates to the control of macrophage recruitment and survival. BALB/c mice were sensitized and challenged with ovalbumin. Three hours before challenge an anti-mouse IL-17 mAb (a-IL-17) was administered. Sampling was conducted 24 h after the allergen challenge. In vitro chemotaxis assay for blood monocytes and culture of airway macrophages, immunocytochemistry for Fas-antigen, and matrix metalloproteinase-9 (MMP-9) were used to determine the effect of IL-17 on the recruitment, survival, and activity of airway macrophages. A-IL-17 reduced the number of airway neutrophils and macrophages after allergen challenge. In vitro, recombinant IL-17 induced migration of blood monocytes and prolonged survival of airway macrophages. A-IL-17 also increased the expression of Fas-antigen in airway macrophages in vivo. Finally, the expression of MMP-9 by airway neutrophils and macrophages in vivo was downregulated by a-IL-17. This study indicates that endogenous IL-17 mediates the accumulation of macrophages during allergen-induced airway inflammation. IL-17 exerts its effects by acting directly on airway macrophages by promoting their recruitment and survival. Furthermore, IL-17 is involved in controlling the proteolytic activity of macrophages and neutrophils in allergen-induced airway inflammation.
Key Words: mice • asthma • neutrophil • matrix metalloproteinase-9 • apoptosis This article has been cited by other articles:
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