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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

Nyckelord

Animals

Apoptosis/immunology

Asthma/immunology

Bronchoalveolar Lavage Fluid/cytology/immunology

Cell Survival/immunology

Cells

Cultured

Chemotaxis

Leukocyte/immunology

Interleukin-17/*immunology/metabolism

Macrophages

Alveolar/*cytology/*immunology/metabolism

Matrix Metalloproteinase 9/metabolism

Mice

Mice

Inbred BALB C

Neutrophils/immunology/metabolism

Pneumonia/*immunology

Publikations- och innehållstyp

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