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Mouse paneth cell secretory responses to cell surface glycolipids of virulent and attenuated pathogenic bacteria.

ABSTRACT: Mouse Paneth cells respond to bacteria and bacterial cell surface antigens by discharging secretory granules into the lumen of small intestinal crypts (T. Ayabe et al., Nat. Immunol. 1:113-118, 2000). To investigate mechanisms regulating these responses, purified surface glycolipid molecules with known acyl chain modifications and attenuated properties were tested for the ability to stimulate Paneth cell secretion. The antigens included lipopolysaccharide (LPS) from wild-type and msbB-null Escherichia coli and phoP-null and phoP-constitutive Salmonella enterica serovar Typhimurium strains, as well as LPS, lipid A, and lipoteichoic acid from Pseudomonas aeruginosa and Listeria monocytogenes grown in Mg2+-limited media. Measurements of total secreted protein, secreted lysozyme, and the bactericidal peptide activities of collected secretions showed that the purified antigens elicited similar secretory responses from Paneth cells in mouse crypts ex vivo, regardless of glycolipid acyl chain modification. Despite their impaired Tlr4 pathway, Paneth cells in ex vivo C3H/HeJ mouse crypts released equivalent amounts of bactericidal peptide activity in response to purified bacterial antigens, including lipid A. Thus, mouse Paneth cells respond equivalently to purified bacterial cell envelope glycolipids, regardless of functional Tlr4, the structural properties of glycolipid acyl chains, or their association with virulence in humans.

SUBMITTER: Tanabe H

PROVIDER: S-EPMC1087394 | biostudies-literature | 2005 Apr

REPOSITORIES: biostudies-literature

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Mouse paneth cell secretory responses to cell surface glycolipids of virulent and attenuated pathogenic bacteria.

Tanabe Hiroki H Ayabe Tokiyoshi T Bainbridge Brian B Guina Tina T Ernst Robert K RK Darveau Richard P RP Miller Samuel I SI Ouellette Andre J AJ

Infection and immunity 20050401 4

Mouse Paneth cells respond to bacteria and bacterial cell surface antigens by discharging secretory granules into the lumen of small intestinal crypts (T. Ayabe et al., Nat. Immunol. 1:113-118, 2000). To investigate mechanisms regulating these responses, purified surface glycolipid molecules with known acyl chain modifications and attenuated properties were tested for the ability to stimulate Paneth cell secretion. The antigens included lipopolysaccharide (LPS) from wild-type and msbB-null Esche ...[more]

PMID: 15784576

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Project description:BACKGROUND:Carcinomas composed predominantly or purely of malignant Paneth cells were rarely reported in gastrointestinal system. They have not been reported at gastroesophageal junction nor has the association with Barrett esophagus been explored. None of the previous studies has mentioned any peculiar histologic features other than typical adenocarcinoma containing neoplastic Paneth cells. The Her2/neu status and the expression of beta-catenin in Paneth cell carcinoma at gastroesophageal junction have not been studied although the activated beta-catenin pathway was recently demonstrated in neoplastic Paneth cells in colon. CASE PRESENTATION:A 70-year-old Caucasian male who initially presented in the emergency room due to upper gastrointestinal bleeding was subsequently found to have a submucosal nodule at gastroesophageal junction. A diagnosis of adenocarcinoma was rendered on biopsy. Histologic examination of the subsequent endoscopic mucosal resection revealed an adenocarcinoma with various levels of differentiation which are zonally distributed. The deeper portion of the tumor showed well-differentiated bland-appearing glands with extensive cystic and secretory changes. The cytoplasm of tumor cells and secretion demonstrated marked reactivity with lysozyme antibody on immunohistochemical stain. The tumor had a peculiar Her2/neu staining pattern with cytoplasmic and nuclear stain in poorly-differentiated area and no stain in well-differentiated area. Only membranous stain was detected with beta-catenin antibody. CONCLUSION:We reported the first case of Paneth cell carcinoma at gastroesophageal junction. The tumor had well-differentiated area which, when sampled in small biopsies, can mimic benign lesions including those related to proton pump inhibitor therapy. Lysozyme immunohistochemical stain may be helpful when difficulty in diagnosis arises. Her-2/neu was negative but showed a distinct staining pattern. In contrast to neoplastic Paneth cells in colon, beta-catenin pathway did not seem to be activated. More studies are needed for the etiology, pathogenesis, clinical course, prognosis and treatment of Paneth cell carcinoma.

Dataset Information

Mouse paneth cell secretory responses to cell surface glycolipids of virulent and attenuated pathogenic bacteria.

Publications

Mouse paneth cell secretory responses to cell surface glycolipids of virulent and attenuated pathogenic bacteria.

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