PP-020-09 Protective role of mast cell chymase in house dust mite induced allergic airway inflammation

• Mast cells release substantial amounts of active proteases, including chymase, upon activation and degranulation inresponse to e.g. IgE cross-linking. A chymase polymorphism has been associated with allergic asthma but the role of chymase in the pathogenesis is not fully understood. We recently showed that mouse mast cell protease 4 (mMCP-4) is the major chymotryptic enzyme in murine airways and that mMCP-4 can protect against bronchial hyperresponsiveness. We here assessed the role of chymase in a model of airway inflammation where mMCP-4 deficient (mMCP-4-/-) and wild type (WT) controls received repeated intranasal instillations of house dust mite (HDM). HDM-sensitization resulted in an accumulation of eosinophils and lymphocytes in the airways of both WT and mMCP-4-/- mice, but the numbers of eosinophils were approximately 5-fold higher in mMCP-4-/- mice. The airway inflammation correlated with the degree of T cell activation in draining lymph nodes. Moreover, the serum level of IgE was significantly higher in sensitized mMCP-4-/- mice than in WT mice. These results suggest a regulatory role for mMCP-4 in the early sensitization process when release of MC proteases in response to IgE cross-linking would be minimal. However, we found that HDM extract per se induced a low but significant degranulation in cultured MCs derived from both mMCP-4-/- and WT mice. Together these results suggest that MC chymase is released upon HDM exposure and that chymase has a protective role in HDM-induced airway inflammation by acting as a negative regulator of allergic sensitization.

Ämnesord

NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

LANTBRUKSVETENSKAPER  -- Veterinärmedicin -- Medicinsk biovetenskap (hsv//swe)

AGRICULTURAL SCIENCES  -- Veterinary Science -- Medical Bioscience (hsv//eng)

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