Volume 127, Issue 1, Pages 155-165 (July 2004) Mouse mast cell protease-1 is required for the enteropathy induced by gastrointestinal helminth infection in the mouse  Catherine E. Lawrence, Yvonne Y.W. Paterson, Steven H. Wright, Pamela A. Knight, Hugh R.P. Miller  Gastroenterology  Volume 127, Issue 1, Pages 155-165 (July 2004) DOI: 10.1053/j.gastro.2004.04.004

Figure 1 Delayed parasite expulsion and decreased enteropathy in mast cell-deficient W/Wv mice. (A) Mice were infected with 400 T. spiralis muscle larvae and worm burdens assessed on day 6 and day 13 postinfection (p.i.) Adult worm burdens are represented as mean ± SEM. (B and C) Crypt lengths and villus lengths (B) and number of mitotic figures/crypt (C) were measured at days 6 and 13 p.i. (D) MPO activity was determined in frozen small intestinal tissue at days 6 and 13 p.i. (E) Levels of apoptosis in 20 small intestine villus/crypt units were measured by TUNEL staining. Uninfected mice are represented at day 0. Results are shown as mean ± SEM. ∗∗Significantly different from day 6 p.i. (P < 0.05). ∗Significant difference between infected and uninfected animals (P < 0.05). †Significant difference between wild-type and W/Wv mice (P < 0.05). Five mice were used per group. Figure is representative of 2 experiments. Gastroenterology 2004 127, 155-165DOI: (10.1053/j.gastro.2004.04.004)

Figure 2 Decreased Th2 responses in mast cell-deficient W/Wv mice. Suspensions of MLN cells were stimulated in the presence of 50 μg/mL T. spiralis antigen for 24 hours. Supernatants were analyzed by sandwich ELISA for the presence of IL-4 (A) or IFN-γ (B). Total serum IgE (C) and T. spiralis antigen-specific IgG1 and IgG2a (D) were determined by ELISA. Uninfected mice are represented at day 0. Five mice were used per group. Data expressed as mean ± SEM. ∗Infected mice significantly different from uninfected mice (P < 0.05), †wild-type mice significantly different from W/Wv mice (P < 0.05). Figure is representative of 2 experiments. Gastroenterology 2004 127, 155-165DOI: (10.1053/j.gastro.2004.04.004)

Figure 3 Decreased proinflammatory responses in mast cell-deficient W/Wv mice. Serum was analyzed for the presence of (A) TNF-α by sandwich ELISA or (B) for nitrite/nitrate by the Greiss assay at 6 and 13 days p.i. Uninfected mice are represented at day 0. Five mice were used per group. Data expressed as mean ± SEM. ∗Infected mice significantly different from uninfected mice (P < 0.05), †wild-type mice significantly different from W/Wv mice (P < 0.05). Figure is representative of 2 experiments. Gastroenterology 2004 127, 155-165DOI: (10.1053/j.gastro.2004.04.004)

Figure 4 Amelioration of pathology in mMCP-1−/− mice. (A and B) Crypt lengths and villus lengths (A) and number of mitotic figures/crypt (B) were measured at days 0, 6, and 13 p.i. (C) MPO activity was determined in frozen small intestine tissue at days 0 and 13 p.i. (D) Levels of apoptosis in 20 small intestine villus/crypt units were measured by TUNEL staining. Uninfected mice are represented at day 0. Results are shown as mean ± SEM. ∗Significant difference between infected and uninfected animals (P < 0.05). †Significant difference between mMCP-1+/+and mMCP-1−/− (P < 0.05). Five mice were used per group. Figure is representative of 2 experiments. Gastroenterology 2004 127, 155-165DOI: (10.1053/j.gastro.2004.04.004)

Figure 5 Equivalent Th2 responses in mMCP-1 −/− mice. Suspensions of MLN cells were stimulated in the presence of 50 μg/mL T. spiralis antigen for 24 hours. Supernatants were analyzed by sandwich ELISA for the presence of IL-4 (A) or IFN-γ (B). Total serum IgE (C) and T. spiralis antigen-specific IgG1 and IgG2a (D) were determined by ELISA. Uninfected mice are represented at day 0. Five mice were used per group. Data expressed as mean ± SEM. ∗Infected mice significantly different from uninfected mice (P < 0.05), †Significant difference between mMCP-1+/+and mMCP-1−/− mice (P < 0.05). Figure is representative of 2 experiments. Gastroenterology 2004 127, 155-165DOI: (10.1053/j.gastro.2004.04.004)

Figure 6 Decreased proinflammatory responses in mMCP-1−/− mice. Serum was analyzed for the presence of (A) TNF-α by sandwich ELISA or (B) for nitrite/nitrate by the Greiss assay at 0, 6, and 13 days p.i. Uninfected mice are represented at day 0. Five mice were used per group. Data expressed as mean ± SEM. ∗Infected mice significantly different from uninfected mice (P < 0.05), †Significant difference between mMCP-1+/+ and mMCP-1−/− mice (P < 0.05). Figure is representative of 2 experiments. Gastroenterology 2004 127, 155-165DOI: (10.1053/j.gastro.2004.04.004)