Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the involvement of adhesion molecules in the lymphocyte infiltration associated with acute intestinal graft-versus-host disease (GVHD) induced by injection of C3H lymph node cells into irradiated (C3H x DBA/2)F1 mice. First we analyzed the expression profile of adhesion molecules including alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, alpha L and beta 7 integrins, CD44 and L-selectin of lymphocytes from lymph nodes and gut mucosa in normal mice. In normal mice, intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) uniquely showed increased expression of alpha 1, alpha 2 and beta 7 integrins, and decreased expression of L-selectin compared with that of lymphocytes of the lymph nodes and Peyer's patches. In mice with GVHD, IEL and LPL of donor lymph node cells origin underwent phenotypic changes characterized by the increased expression of alpha 1, alpha L and beta 7 integrins, and the loss of L-selectin. The expression profile of adhesion molecules on IEL and LPL of GVHD mice resembled that of normal mice except for the lack of alpha 2 integrin. Treatment of GVHD mice with anti-alpha 1, -alpha 4 or -beta 7 integrin antibody alone partially prevented the mucosal pathology of intestinal GVHD, whereas only mice treated with anti-alpha 1 showed reduced donor lymphocytic infiltration into the intestinal mucosa. In contrast, treatment with anti-alpha L or anti-CD44 antibody did not affect the intestinal GVHD. Furthermore, dual blockade of both alpha 1 and alpha 4 integrins completely inhibited the mucosal pathology and donor lymphocyte infiltration of intestinal GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of alpha 1 and alpha 4 integrins in gut mucosal injury of graft-versus-host disease. 749 25

Expansion of the glomerular mesangial matrix (MM), thickening of the glomerular basement membrane (GBM), and eventually the development of glomerulosclerosis are often seen in immunologically mediated kidney diseases. In addition to quantitative changes in the extracellular matrix (ECM), qualitative changes in ECM molecules may contribute to alterations in the composition of the glomerular matrix. The expression of collagen IV, alpha 1-5(IV) mRNA, and polypeptides was therefore investigated during the development of chronic graft-versus-host disease (GvHD) in mice, a model for lupus nephritis, and in chronic serum sickness (CSS) in rats, a model for membranous nephropathy. Immunohistochemical studies showed increased mesangial expression of alpha 1 and alpha 2 early in the disease, but only late in the GBM. In contrast, alpha 3 and alpha 4 increased in the GBM during disease, but not in the MM. The mRNA levels for all collagen IV chains were increased in isolated glomeruli before morphological alterations were detectable. The mRNA increase was earlier and more profound for alpha 3, alpha 4 and alpha 5 than for alpha 1 and alpha 2. Expression of alpha 3(IV) was greatest in GvHD, whereas expression of alpha 4 was greatest in CSS. As determined by in situ hybridization (ISH), alpha 1 mRNA was observed dispersed in the glomerulus, but alpha 3, alpha 4, and alpha 5 mRNAs were mainly located in cells at the periphery of the glomerular tuft. The changes in the relative abundance of collagen IV mRNA in disease states may perturb the collagen IV network, altering glomerular structure and function, and may thereby play a central role in the development of glomerulonephritis and glomerulosclerosis.
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PMID:Differential expression of collagen IV isoforms in experimental glomerulosclerosis. 961 84