Depletion of mucosal mast cell protease by corticosteroids: effect on intestinal anaphylaxis in the rat

Abstract

Rats primed by infection with the intestinal nematode Nippostrongylus brasiliensis and challenged intravenously with soluble whole-worm antigen undergo systemic anaphylactic shock. The primary lesions are in the gut and include increased permeability of the mucosa together with release, into enteric secretions, of a mucosal mast cell (MMC)-specific serine proteinase, rat mast cell protease II (RMCP-II). This enzyme is also released into the blood of shocked rats. These manifestations of anaphylaxis were abolished in rats previously treated with corticosteroids (methylprednisolone acetate, 25 mg per kg of body weight, 48 and 24 hr before i.v. challenge with antigen). Suppression of the response was associated with depletion of RMCP-II and of MMC from the intestinal mucosa. Depletion occurred 4-24 hr after treatment with as little as 1 mg of methylprednisolone per kg. By contrast, neither connective tissue mast cells nor serum levels of parasite-specific IgE were depleted in rats given 2 X 25 mg of methylprednisolone per kg. The capacity of unprimed treated rats to mount passive cutaneous anaphylaxis was, however, impaired.