Expulsion of gastrointestinal nematodes is associated with pronounced mucosal mast cell (MMC) hyperplasia, differentiation, and activation, accompanied by the systemic release of MMC granule chymases (chymotrypsin-like serine proteases). The β-chymase mouse mast cell protease-1 (mMCP-1) is expressed predominantly by intraepithelial MMCs, and levels in the bloodstream and intestinal lumen are maximal at the time of worm expulsion in parasitized mice. To address the in vivo functions of MMC-specific β-chymases, we have generated transgenic mice that lack the mMCP-1 gene. They were backcrossed onto a congenic BALB/c background to investigate the response to nematode infection. The deletion of the mMCP-1 gene is associated with significantly delayed expulsion of Trichinella spiralis and increased deposition of muscle larvae in BALB/c mice despite the presence of normal and sometimes increased numbers of MMCs. Neither worm fecundity nor worm burdens were altered in Nippostrongylus-infected mMCP-1−/− BALB/c mice. These data demonstrate, for the first time, that the ablation of an MMC-derived effector molecule compromises the expulsion process.

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A mouse monoclonal antibody (MoAb), reactive with a repetitive carbohydrate epitope on lentil-lectin adherent glycoproteins present on the surface and in the secretions of Taenia saginata cysticerci, was used in the construction of a diagnostic ELISA assay to detect these glycoproteins in the serum of T. saginata infected cattle. The MoAb was used as the trapping layer and subsequently bound glycoprotein was revealed using the same MoAb and biotinylated peroxidase-streptavidin complex as the developing system. The assay was suitably specific. Exceptionally low background values were obtained with sera from animals with a range of commonly occurring tropical parasitic infections, including Taenia hydatigena, Echinococcus granulosus and Fasciola gigantica. The minimal detection level was approximately 200 live cysticerci in cattle. Parasite derived glycoprotein could be detected in serum from about 4-5 weeks post-infection onwards and was associated with a current infection, as drug treatment of infected cattle to kill the cysticerci resulted in the disappearance of these components from the circulation, while the titre of anti-parasite antibody remained high. The same assay also detected Taenia solium cysticercosis in humans.

Intestinal mucosal mast cells (IMMC) express granule neutral proteases that are regulated by T-cell–derived cytokines, including interleukin-3 (IL-3) and IL-9, and by stem cell factor (SCF). The IMMC-specific chymase, mouse mast cell protease-1 (mMCP-1), is released in substantial quantities into the blood stream during gastrointestinal allergic responses. We used cultured bone marrow-derived mast cells (mBMMC) to identify cytokines that regulate the expression and extracellular release of mMCP-1. When grown in IL-3–rich WEHI (15% vol/vol) and 50 ng/mL recombinant rat SCF (rrSCF) bone marrow cells supplemented with IL-9 (5 ng/mL) differentiated into mBMMC that expressed a maximum of less than 250 ng mMCP-1/106 cells and 189 ng mMCP-1/mL of culture supernatant. Supplementation of the same three cytokines with transforming growth factor-β1(TGF-β1; 1 ng/mL) resulted in substantially enhanced expression (6 μg/106 mBMMC) and extracellular release (2 μg/mL of culture supernatant) of mMCP-1. The response to TGF-β1 was dose-dependent, with maximal effect at 1 ng/mL, and was associated with immunohistochemical and ultrastructural changes in the secretory granules. IL-9–induced expression of mMCP-1 may be due to endogenously expressed TGF-β1, because it was blocked by anti–TGF-β antibodies. In conclusion, the expression and extracellular release of the IMMC-specific chymase, mMCP-1, is strictly regulated by TGF-β1.