Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6- dependent mechanism1   Anil Mishra, Marc E Rothenberg  Gastroenterology  Volume 125, Issue 5, Pages 1419-1427 (November 2003) DOI: 10.1016/j.gastro.2003.07.007

Figure 1 Kinetic and dose-response analysis of IL-13-induced EE. Wild-type mice were exposed to 5 doses (0.5, 1.0, and 10 μg) of recombinant murine IL-13 delivered by intratracheal administration on consecutive days. The level of eosinophils in the esophagus 24 hours after each dose of IL-13 was quantitated by anti-MBP immunohistochemistry. The data are expressed as mean ± SD (n = 5 or 6 mice at each dose and time point) and are representative of 3 experiments. Gastroenterology 2003 125, 1419-1427DOI: (10.1016/j.gastro.2003.07.007)

Figure 2 Immunohistochemical analysis of IL-13-induced EE. Wild-type mice were exposed to 5 doses of saline (A) or recombinant murine IL-13 (4.0 μg) (B–D) delivered by intratracheal administration on consecutive days. Esophageal tissue was fixed in paraformaldehyde, embedded in paraffin, cut into 5-μm sections, and immunostained with anti-MBP. Representative eosinophils are identified by black staining. Eosinophils are identified only in the IL-13-treated mice and are primarily localized to the lamina propria (lp), but also to the muscularis mucosa (mm), and epithelial (ep) layers. Representative eosinophils are identified with solid arrows, solid arrowheads, and open arrowheads in the lp, ep, and mm regions, respectively. The photomicrographs are representative of 3 experiments. Original magnification 125× for A and B and 400× for C and D. Gastroenterology 2003 125, 1419-1427DOI: (10.1016/j.gastro.2003.07.007)

Figure 3 Epithelial proliferation following IL-13 delivery. Mice (BALB/c) were treated with 5 doses of intratracheal saline or IL-13 (4.0 μg), and the incorporation of BrdU in the epithelial layer was measured 3 hours after the last challenge. (A) A representative photomicrograph showing BrdU+ epithelial cells following IL-13 treatment is shown. (B) Quantification of BrdU incorporation in saline or IL-13-treated mice is shown. The results are mean ± SD (n = 5 or 6 mice) and are representative of 2 experiments. Arrowheads indicate representative BrdU+ cells. Original magnification ×125. Gastroenterology 2003 125, 1419-1427DOI: (10.1016/j.gastro.2003.07.007)

Figure 4 IL-13-induced EE in STAT6 gene-targeted mice. The levels of eosinophils in the esophagus of STAT6 gene-targeted and wild-type mice were analyzed following intratracheal IL-13 treatment. Wild-type (+/+) or STAT6-deficient (−/−) mice were treated with 5 doses of intratracheal control saline (−) or IL-13 (4.0 μg) (+), and the number of eosinophils in the esophagus (A) was determined by anti-MBP staining and in the BALF (B) by differential counting. The results are expressed as mean ± SD (n = 5–7 mice) and are representative of 3 experiments. Gastroenterology 2003 125, 1419-1427DOI: (10.1016/j.gastro.2003.07.007)

Figure 5 IL-13-induced EE in IL-5 gene-targeted mice. The levels of eosinophils in the esophagus of IL-5 gene-targeted and wild-type mice were analyzed following intratracheal IL-13 treatment. Wild-type (+/+) or IL-5-deficient (−/−) mice were challenged with 5 doses of control saline (−) or IL-13 (4.0 μg) (+), and the number of eosinophils in the esophagus (A) was determined by anti-MBP staining and in the BALF (B) by differential counting. The results are expressed as mean ± SD (n = 5 or 6 mice) and are representative of 2 experiments. Gastroenterology 2003 125, 1419-1427DOI: (10.1016/j.gastro.2003.07.007)

Figure 6 IL-13-induced EE in eotaxin-1 gene-targeted mice. The levels of eosinophils in the esophagus of eotaxin-1 gene-targeted and wild-type mice were analyzed following intratracheal IL-13 treatment. Wild-type (+/+) or eotaxin-1-deficient (−/−) mice were treated with 5 doses of control saline (−) or IL-13 (4.0 μg) (+), and the number of eosinophils in the esophagus (A) was determined by anti-MBP staining and in the BALF (B) by differential counting. The results are expressed as mean ± SD (n = 4 or 5 mice) and are representative of 3 experiments. Gastroenterology 2003 125, 1419-1427DOI: (10.1016/j.gastro.2003.07.007)