Dysplastic polyps in chronic colitis: is colectomy needed?
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Colectomy↗
Biomedical subjects
J M Klapproth
Publications and source records attributed to J M Klapproth.
A large toxin from pathogenic Escherichia coli strains that inhibits lymphocyte activation.
The mechanisms by which bacteria resist cell-mediated immune responses to cause chronic infections are largely unknown. We report the identification of a large gene present in enteropathogenic strains of Escherichia coli (EPEC) that encodes a toxin that specifically inhibits lymphocyte proliferation and interleukin-2 (IL-2), IL-4, and gamma interferon production in response to a variety of stimuli. Lymphostatin, the product of this gene, is predicted to be 366 kDa and shares significant homology with the catalytic domains of the large clostridial cytotoxins. A mutant EPEC strain that has a disruption in this gene lacks the ability to inhibit lymphokine production and lymphocyte proliferation. Enterohemorrhagic E. coli strains of serotype O157:H7 possess a similar gene located on a large plasmid. Loss of the plasmid is associated with loss of the ability to inhibit IL-2 expression while transfer of the plasmid to a nonpathogenic strain of E. coli is associated with gain of this activity. Among 89 strains of E. coli and related bacteria tested, lifA sequences were detected exclusively in strains capable of attaching and effacing activity. Lymphostatin represents a new class of large bacterial toxins that blocks lymphocyte activation.
Bacterial Toxins↗
Major pathways of mucosal immunity and inflammation: cell activation, cytokine production and the role of bacterial factors.
The gastrointestinal mucosal immune system contains a large, complex mixture of cells that play an essential role in host defence against pathogens and in maintaining the normal balance of tolerance and immunity to constituents of the gastrointestinal lumen. Cells are organized in specialized structures: Peyer's patches (which are important in initiating immune responses and in non-organized compartments) and the lamina propria, where specialized, differentiated cells carry out effector functions. Many of the specialized functions of cells in this system depend on the release of cytokines and other mediators. Recent studies have demonstrated the importance of the gastrointestinal flora in modulating the activity of the mucosal immune cells and exacerbating gastrointestinal inflammation. The function of gastrointestinal immune cells and their mediators appear to be altered in inflammatory bowel diseases and offer potential targets for pharmacological intervention.
Animals↗
Products of enteropathogenic E. coli inhibit lymphokine production by gastrointestinal lymphocytes.
Previously we have shown that lysates of enteropathogenic Escherichia coli (EPEC) inhibit lymphokine production by mitogen-activated peripheral blood mononuclear cells (PBMCs). The aim of the present study was to determine whether products of EPEC alter lymphokine expression by gastrointestinal mucosal lymphocytes. Lysates from EPEC clones inhibited mitogen-stimulated interleukin-2 (IL-2), IL-4, IL-5, and interferon-gamma (IFN-gamma) but not IL-8 mRNA expression by lamina propria mononuclear cells isolated from surgically resected colon specimens. Inhibitory lysates did not significantly change CD25 expression on either CD4, CD8, or CD45R0 lymphocytes by flow cytometry. Bacterial supernatants of EPEC inhibited IL-2 and IL-5 protein secretion by mitogen-stimulated PBMCs. EPEC lysates inhibited IL-2 mRNA expression induced by lysates of nonpathogenic E. coli. In conclusion, EPEC contains a novel gene(s) that encodes factors that selectively inhibit IL-2, IL-4, IL-5, and IFN-gamma expression by mucosal mononuclear cells without affecting CD25 or IL-8 expression. Thus enteric bacteria can produce factors that may regulate the function of the gastrointestinal mucosal immune system.
Antigens, CD↗
Products of enteropathogenic Escherichia coli inhibit lymphocyte activation and lymphokine production.
The aim of this study was to determine whether products of enteric bacteria are able to regulate lymphocyte activation and cytokine production. Whole bacteria and bacterial lysates from different strains of Escherichia coli were tested for their ability to inhibit cytokine production by peripheral blood mononuclear cells as determined by reverse transcription-PCR, Northern (RNA) blotting of cellular RNA, or enzyme-linked immunosorbent assay for cytokine protein. Lysates from two pathogenic strains of E. coli, enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli, inhibited mitogen-stimulated expression of interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon. IL-1 beta, IL-6, IL-8, IL-10, IL-12, and Rantes mRNA expression was not affected. The inhibitory activity was dose dependent, protease and heat sensitive, nondialyzable, and not due to cellular toxicity. The inhibitory activity remained in EPEC strains having mutations in known virulence factors. Nonpathogenic E. coli HB101 transformed with a 22-kb cosmid clone derived from EPEC chromosomal DNA expressed the inhibitory activity. Thus, certain strains of pathogenic E. coli express a protein or proteins encoded by chromosomal genes that selectively inhibit lymphocyte activation and lymphokine production. Therefore, immunosuppressive factors produced by pathogenic bacteria could be important in modifying gastrointestinal immune responses in enteric bacterial infections or gastrointestinal autoimmune diseases.
Bacterial Proteins↗