Document Detail

Effects of lymphotoxin beta receptor blockade on intestinal mucosal immunity.
MedLine Citation:
PMID:  17712143     Owner:  NLM     Status:  MEDLINE    
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.
Woodae Kang; Kenneth A Kudsk; Yoshifumi Sano; Jinggang Lan; Fu Yang-Xin; F Enrique Gomez; Yoshinori Maeshima
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
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:
Created Date:  2007-08-22     Completed Date:  2007-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804134     Medline TA:  JPEN J Parenter Enteral Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  358-64; discussion 364-5     Citation Subset:  IM    
Department of Surgery, University of Wisconsin-Madison College of Medicine and Public Health, Madison, Wisconsin, USA.
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MeSH Terms
Enzyme-Linked Immunosorbent Assay / methods
Gene Expression Regulation
Immunity, Mucosal* / physiology
Immunoglobulin A / biosynthesis,  immunology*
Immunoglobulins / metabolism*
Intestine, Small / immunology
Lymphocyte Count
Lymphotoxin beta Receptor / antagonists & inhibitors*,  metabolism
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
Reg. No./Substance:
0/Immunoglobulin A; 0/Immunoglobulins; 0/Lymphotoxin beta Receptor; 0/MADCAM1 protein, human; 0/Mucoproteins; 0/RNA, Messenger

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