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-ll). 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.Corticosteroids are potent, widely used anti-inflammatory drugs, and their therapeutic value in the treatment of allergic conditions in man and domestic animals is well known. Although these drugs act at a number of different levels, perhaps their most significant anti-allergic effect is in preventing the generation and release of inflammatory mediators (1). For example, they suppress histamine release from isolated rat and murine mast cells (2, 3), and they act indirectly to prevent the generation of secondarily formed mediators (4-6).Systemic anaphylaxis in the rat is abrogated by prior treatment of sensitized animals with corticosteroids (7). The major shock organ responding to anaphylaxis in this species is the small intestine (8), and the lesions associated with intestinal anaphylaxis include hyperaemia, secretion of mucus, and epithelial shedding (9-11). The development of intestinal lesions is associated with the release, into the blood circulation and into the gut lumen, of a mucosal mast cell (MMC)-derived neutral proteinase, rat mast cell protease II (RMCP-II) (10,11), and recent studies have implicated this enzyme in the generation of intestinal epithelial permeability (11).Because RMCP-II is a highly soluble product of MMC (12) and is antigenically distinct from insoluble chymotrypsinlike enzyme (RMCP-I) in connective tissue mast cells (13), its release into the blood circulation or gut lumen provides a unique and highly specific marker of in vivo activation of MMC. We have, therefore, measured the concentration of this enzyme within the tissues, in the intestinal secretions, and in blood in order to analyze the anti-anaphylactic activity of corticosteroids and to measure their effect on the mucosal mast cell subpopulation in rats subjected to anaphylactic shock. MATERIALS AND METHODS Animals. Male and female outbred Wistar rats matched for age (30-36 weeks) and weight (350-45...

Inhibitory Effect of Cortisol on the Degranulation of Eosinophilic Granular Cells in Tilapia.

“…We also showed that in vitro degranulation of EGCs induced by substance P or by tilapia normal sera containing zymo san (in which anaphilatoxin was expected to be pro duced) was also suppressed by cortisol. These results indicate a cortisol-mediated direct inactivation of EGCs in fish as has been reported in mammalian mast cells (King et al, 1985). Kurogi and lida (1999) reported that stress suppresses the defense activity of neutrophils, and number of neutrophils that migrated to the site of inflammation was reduced by stress.…”

“…A similar reduction in EGCs by cortisol was reported to occur in mammalian mast cells (King et al, 1985). The mast cells proliferate in response to some cytokines (IL-3, IL -4, Nerve growth factor, etc), which are produced by T lymphocyte or fibroblast (Nechushtan and Razin, 1996).…”

“…A potent inhibitory effect of glucocorti coid on the mammalian mast cell activity has been reported by some investigators (Daeron et al, 1982;King et al, 1985). Cortisol implantation in fish reduced immunological responses and increased the susceptibility to diseases (Pickering and Duston, 1983), as did stress (Wedemeyer, 1997).…”

Corticosteroids in management of anaphylaxis; a systematic review of evidence

“…Most investigated the effect of pretreatment with glucocorticoids. The postulated mechanisms of action include action through modulation of gene expression occurring 4 to 24 hours after treatment with glucocorticoids (48,65) and blockade of signal activation of glucocorticoid receptors independent of its genomic effects (52,53). The latter response has been detectable within 5 to 30 minutes (52,53).…”

“…The animal models used included guinea pigs (62)(63)(64) and mice (48,53,65,66). One other study was conducted using A549 human adenocarcinoma cell line (52).…”