Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats receiving a single dose (10 mg/l00 g body wt) of PAN develop severe proteinuria and acute interstitial nephritis. To investigate the mechanisms involved in interstitial leucocyte accumulation, we examined the expression of adhesion molecules on kidney tissue sections as well as on endothelial cell cultures. We also performed in vivo treatments with antibodies against adhesion molecules. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) was found on day 7 of the disease, when interstitial nephritis was first detected. Also, rat endothelial cells in culture showed maximal expression of ICAM-1 in the presence of 10(-9) - 10(-11) M PAN. Adhesion of peripheral blood mononuclear cells (PBMC) on kidney sections from PAN-treated rats was highest on day 7 (3.05 +/- 0.7 (mean +/- s.e.m.); controls 0.75 +/- 0.5). Such increased adhesion was notably blocked after PAN-treated rat kidney sections were incubated with anti-ICAM-1 MoAb (0.9 +/- 0.4). In addition, adhesiveness of PBMC to PAN-stimulated endothelial cells in culture was enhanced (25 +/- 2.5%; non-stimulated cells 13 +/- 3.1%). The addition of specific MoAbs against ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) produced a high blockage of adhesiveness induced by exposure to PAN (inhibition 58 +/- 3%; non-stimulated cells 40 +/- 7%). Simultaneous administration to PAN-treated rats of anti-LFA-1 and anti-ICAM-1 MoAbs reduced the number of interstitial cells by 70% compared with the 30% of reduction obtained when anti-very late antigen-4 (VLA-4) MoAb and anti-vascular cell adhesion molecule-1 (VCAM-1) antibodies were used. Our results suggest that the LFA-1/ICAM-1 pathway plays a principal role in the interstitial nephritis occurring in rats with PAN-nephrosis.
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PMID:Role of leucocyte adhesion molecules in aminonucleoside of puromycin (PAN)-associated interstitial nephritis. 909 15

Extensive flattening of podocyte foot processes and increased permeability of the glomerular capillary filter are the major pathologic features of minimal change nephrosis (MCN) and focal segmental glomerulosclerosis (FSGS). Adhesion proteins anchor and stabilize podocytes on the glomerular basement membrane (GBM), and presumably are involved in the pathogenesis of foot process flattening. Thus far, ao3 P,-integrin was localized to basal cell membrane domains. In this report, ao- and 3-dystroglycan (DG) were detected at precisely the sa-ne location by immunoelectron microscopy. and the presence of ac- and /-DG chains was confirmed by immunoblotting on isolated human glomeruli. Because the major DG binding partners in the GBM (laminin, agrin, perlecan), and the intracellular dystrophin analogue utrophin are also present in glomeruli, it appears that podocytes adhere to the GBM via DG complexes, similar to muscle fibers in which actin is linked via dystrophin and DG to the extracellular matrix. As with muscle cells, it is therefore plausible that podocytes use precisely actin-guided DG complexes at their "soles" to actively govern the topography of GBM matrix proteins. Expression of the a//3-DG complex was reported to be reduced in muscular dystrophies. and therefore a search for similar pathologic alterations in archival kidney biopsies from patients with MCN (it = 16) and FSGS (ni = 8) was conducted by quantitative immunoelectron microscopy. The density of a-DG on the podocyte's soles was significantly reduced to 25% in MCN, whereas it was not different in normal kidneys and FSGS. The expression of 3-DG was reduced to >50% in MCN, and was slightly increased in FSGS. Levels of DG expression returned to normal in MCN after steroid treatment (7 = 4). Expression of /3-integrin remained at normal levels in all conditions. These findings point to different potentially pathogenic mechanisms of foot process flattening in MCN and FSGS.
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PMID:Glomerular expression of dystroglycans is reduced in minimal change nephrosis but not in focal segmental glomerulosclerosis. 1070 64