Backleak, tight junctions, and cell- cell adhesion in postischemic injury to the renal allograft
| Autor: | W J Nelson, Osun Kwon, Bryan D. Myers, Donald C. Dafoe, Richard K. Sibley, Edward J. Alfrey, John D. Scandling, P. Huie |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Biology Kidney Function Tests Tight Junctions Adherens junction Ischemia Cell Adhesion medicine Humans Transplantation Homologous Cell adhesion Basement membrane Tight junction Inulin Membrane Proteins General Medicine Acute Kidney Injury Middle Aged Phosphoproteins Kidney Transplantation Transplantation Cytoskeletal Proteins Microscopy Electron Kidney Tubules medicine.anatomical_structure Tubule Microscopy Fluorescence Reperfusion Injury Paracellular transport Catenin Immunology Zonula Occludens-1 Protein Female Research Article |
| Zdroj: | Journal of Clinical Investigation. 101:2054-2064 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci772 |
| Popis: | Postischemic injury in recipients of 3-7-d-old renal allografts was classified into sustained (n = 19) or recovering (n = 20) acute renal failure (ARF) according to the prevailing inulin clearance. Recipients of optimally functioning, long-standing allografts and living donors undergoing nephrectomy served as functional (n = 14) and structural controls (n = 10), respectively. Marked elevation above control of fractional clearance of dextrans of graded size was consistent with transtubular backleak of 57% of filtrate (inulin) in sustained ARF. No backleak was detected in recovering ARF. To explore a structural basis for backleak, allograft biopsies were taken intraoperatively, 1 h after reperfusion in all recipients, and again on day 7 after transplant in a subset (n = 10). Electron microscopy revealed disruption of both apical and basolateral membranes of proximal tubule cells in both sustained and recovering ARF, but cell exfoliation and tubule basement membrane denudation were negligible. Histochemical analysis of membrane-associated adhesion complexes confirmed an abnormality of proximal but not distal tubule cells, marked in sustained ARF but not in recovering ARF. Staining for the zonula occludens complex (ZO-1) and adherens complex (alpha, beta, and gamma catenins) revealed diminished intensity and redistribution of each cytoskeletal protein from the apico-lateral membrane boundary. We conclude that impaired integrity of tight junctions and cell-cell adhesion in the proximal tubule provides a paracellular pathway through which filtrate leaks back in sustained allograft ARF. |
| Databáze: | OpenAIRE |
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