| Effects of lymphotoxin beta receptor blockade on intestinal mucosal immunity. | |
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MedLine Citation:
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PMID: 17712143 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) directs lymphocyte migration into gut-associated lymphoid tissue (GALT) through Peyer's patches (PPs). Parenteral nutrition (PN) impairs mucosal immunity by reducing PPs MAdCAM-1 expression, T and B cells in GALT, and intestinal and respiratory immunoglobulin (Ig) A levels. We previously showed that PN reduces lymphotoxin beta receptor blockade (LTbetaR) in PPs and intestine, and that stimulation with LTbetaR agonist antibodies reverses these defects. To confirm that LTbetaR regulates transcription of MAdCAM-1 message and more fully understand the effects of LTbetaR on MAdCAM-1 function within the mucosal immune system, we studied the effect of LTbetaR blockade with a chimeric LTbetaR Ig-fusion protein on MAdCAM-1 mRNA levels, PP lymphocyte mass and IgA levels in the intestinal and respiratory tracts. METHODS: Mice were cannulated and killed 3 days after receiving chow + control Ig, chow + LTbetaR-Ig fusion protein (100 microg IV), or PN + control Ig. The PPs of half of the animals were processed for lymphocyte count, and the other half were processed for complementary DNA and subsequent polymerase chain reaction (PCR). mRNA levels of MAdCAM-1 were determined by real-time PCR; intestinal and respiratory IgA levels were measured by ELISA. RESULTS: PN significantly reduced PP lymphocyte mass, MAdCAM-1 mRNA, and intestinal IgA. As anticipated, LTbetaR blockade significantly decreased PP cells and MAdCAM-1 mRNA, but not intestinal IgA because chow feeding was maintained. Both LTbetaR blockade and PN decreased nasal IgA, but not significantly. CONCLUSIONS: LTbetaR blockade in chow animals significantly reduces transcription of MAdCAM-1 gene and PPs lymphocyte mass. These data implicate inadequate LTbetaR signaling as a major mechanism for decreased GALT cells with lack of enteral stimulation, and further establish the role of LTbetaR in the mucosal immune system. |
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Authors:
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Woodae Kang; Kenneth A Kudsk; Yoshifumi Sano; Jinggang Lan; Fu Yang-Xin; F Enrique Gomez; Yoshinori Maeshima |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: JPEN. Journal of parenteral and enteral nutrition Volume: 31 ISSN: 0148-6071 ISO Abbreviation: JPEN J Parenter Enteral Nutr Publication Date: 2007 Sep-Oct |
Date Detail:
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Created Date: 2007-08-22 Completed Date: 2007-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7804134 Medline TA: JPEN J Parenter Enteral Nutr Country: United States |
Other Details:
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Languages: eng Pagination: 358-64; discussion 364-5 Citation Subset: IM |
Affiliation:
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Department of Surgery, University of Wisconsin-Madison College of Medicine and Public Health, Madison, Wisconsin, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Enzyme-Linked Immunosorbent Assay / methods Gene Expression Regulation Humans Immunity, Mucosal* / physiology Immunoglobulin A / biosynthesis, immunology* Immunoglobulins / metabolism* Intestine, Small / immunology Lymphocyte Count Lymphotoxin beta Receptor / antagonists & inhibitors*, metabolism Male Mice Mice, Inbred ICR Mucoproteins / metabolism* Parenteral Nutrition / adverse effects* Peyer's Patches / cytology, immunology*, metabolism Polymerase Chain Reaction / methods RNA, Messenger / metabolism Random Allocation |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM53439/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Immunoglobulin A; 0/Immunoglobulins; 0/Lymphotoxin beta Receptor; 0/MADCAM1 protein, human; 0/Mucoproteins; 0/RNA, Messenger |
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