Interleukin-17 as a recruitment and survival factor for airway macrophages in allergic airway inflammation.
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.
Sergejeva
Svetlana
S
The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden. Svetlana.Sergejeva@lungall.gu.se
Ivanov
Stefan
S
Lötvall
Jan
J
Lindén
Anders
A
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001249:Asthma / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology*
D020381:Interleukin-17; D020780:Matrix Metalloproteinase 9