Interleukin-17 as a recruitment and survival factor for airway macrophages in allergic airway inflammation

Am J Respir Cell Mol Biol. 2005 Sep;33(3):248-53. doi: 10.1165/rcmb.2004-0213OC. Epub 2005 May 18.

Abstract

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.

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Asthma / immunology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Survival / immunology
  • Cells, Cultured
  • Chemotaxis, Leukocyte / immunology
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Macrophages, Alveolar / cytology*
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Pneumonia / immunology*

Substances

  • Interleukin-17
  • Matrix Metalloproteinase 9