Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in rat

Abstract

Infestation of the gastrointestinal tract by parasitic nematodes is invariably associated with mucosal mastocytosis, which is a thymus-dependent phenomenon in parasitized rats, and is adoptively transferable with a T cell-enriched population of thoracic duct lymphocytes. When derived by in vitro culture, mucosal mast cells (MMC) arise from a bone marrow precursor after stimulation by T cell-derived factors. In rats infected with the nematode Trichinella spiralis, mucosal mastocytosis is temporally associated with the immune expulsion of the adult worms whereas in the case of Nippostrongylus brasiliensis, mastocytosis is frequently observed to occur after worm expulsion has been completed. Consequently, there has been doubt as to whether MMC are active and serve a functional role in the expulsion of rat intestinal nematodes. MMC contain and secrete a neutral proteinase, rat mast cell protease II (RMCP II); detection and assay of secreted RMCP II therefore provides a direct measurement of MMC activity. Here we describe the release of this enzyme into the blood of rats infected with N. brasiliensis or T. spiralis. Our results show that the systemic secretion of RMCP II coincides with the immune expulsion of these nematodes, demonstrating clearly for the first time that rat MMC are functionally active during the immune elimination of primary nematode infections.

A Role of Mast Cell Glycosaminoglycans for the Immunological Expulsion of Intestinal Nematode, Strongyloides venezuelensis

“…In addition, S. venezuelensis adult worms are not expelled in Mongolian gerbils, in which mucosal mast cells never migrate into the intestinal epithelia (44,45). Mucosal mast cells release their granular contents upon antigenic stimulation (8,46), but the mode of degranulation might be different from that in connective tissue mast cells. It is known in mice that mucosal mast cells show characteristic paracrystallization of their granular contents in intestinal nematode infections (47,48).…”

“…In rats, reserpininduced sulfated intestinal goblet cell mucin inhibits establishment of implanted adult worms (15). Mast cell glycosaminoglycans are highly sulfated (16 -18), and granular contents are released into the intestinal lumen during worm expulsion (8). Thus, glycosaminoglycans in the secretory granules of mucosal mast cells are primary candidates for effector molecules in S. venezuelensis expulsion.…”

Expulsion of Secondary Trichinella spiralis Infection in Rats Occurs Independently of Mucosal Mast Cell Release of Mast Cell Protease II

“…In both mice and rats, primary infection induces a potent Th2 response leading to intestinal mastocytosis (1). Mast cell degranulation can be detected at the time of adult worm expulsion (2)(3)(4). The temporal alignment of intestinal mastocytosis and mast cell degranulation with the rejection of adult worms provided evidence that mast cells may be key to intestinal defense against the parasite.…”

Muscularis mucosae - the forgotten sibling

“…We have demonstrated that large numbers of mucosal mast cells were found in the lamina propria and muscularis mucosae, but scarcely in the epithelium and external muscles of the mammalian ileum (Fujinuma et al, 1986). Furthermore, Woodbury et al (1984) had reported that the number of mucosal mast cells per villus crypt in the rat duodenum increased with parasitosis. The mucosal mast cells may therefore function as an expulsion system of intestinal nematode infections.…”