Serine protease activity of Per a 10 augments allergen-induced airway inflammation in a mouse model

V T Sudha, N Arora, B P Singh
European Journal of Clinical Investigation 2009, 39 (6): 507-16

BACKGROUND: We recently reported an immunodominant serine protease allergen (Per a 10) from Periplaneta americana. This study investigates the role of its proteolytic activity in driving the immune responses towards self and other allergens.

MATERIALS AND METHODS: Groups of Balb/c mice were sensitized intraperitoneally and subcutaneously with proteolytically active Per a 10 or inactivated Per a 10 (using aminoethyl benzenesulfonyl fluoride hydrochloride) or whole body P. americana extract and subsequently challenged intranasally with the respective antigens. Mice were also sensitized and challenged with ovalbumin (OVA) alone or co-administered with active or inactive Per a 10. The immune-inflammatory responses were measured by airway hyperresponsiveness (AHR) and cellular infiltration of lungs i.e. eosinophil counts, eosinophil peroxidase (EPO) activity, myeloperoxidase activity (MPO), lung histopathology, serum levels of specific-antibodies and levels of Th1/Th2 interleukins in bronchoalveolar lavage fluid (BALF) and in spleen cells culture supernatant.

RESULTS: Mice challenged with active Per a 10/P. americana extract showed a significant airway inflammation demonstrated by enhanced AHR and increased cellular infiltration of lungs as evidenced by high eosinophil counts, EPO activity, IL-4 and IL-5 in BALF. Active Per a 10 also induced a significant proliferation of spleen cells, increased secretion of IL-4 and IL-5 in the spleen cells culture supernatant and systemic production of specific-IgE and IgG1. However, exposure with inactive Per a 10 elicited a low cellular infiltration and systemic antibody production. Exposure to OVA with active Per a 10 demonstrated a significantly high cellular infiltration and production of OVA-specific IgE and IgG1, than exposure to OVA alone or with inactive Per a 10.

CONCLUSIONS: Proteolytic activity of Per a 10 plays an important role in driving the allergic immune response by providing an adjuvant effect, towards self and other potential allergens present in the same microenvironment.


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