Determinants of glomerular mesangial localization of immune complexes. Role of endothelial fenestrae

W. F. Keane, L. Raij

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Abstract

Morphologic studies with macromolecular tracers have suggested that immune complexes may gain access to the glomerular mesangium by passage through endothelial fenestrae. If this assumption is correct, a reduction in endothelium fenestrae number and/or surface area should decrease glomerular capillary lumen-mesangial traffic of immune complexes. In rats, nephrotoxic acute renal failure (ARF) induced by either gentamicin or uranyl nitrate is accompanied by a 50 per cent reduction in the number and a 70 per cent decrease in the surface area of glomerular endothelial fenestrae. These morphologic alterations correlate with a decrease in the glomerular filtration rate and in the glomerular ultrafiltration coefficient. Thus, we wished to evaluate the influence that these endothelial fenestral changes could have on the lumen-mesangial traffic of immune complexes. For that purpose, we studied mesangial uptake and disappearance of radiolabeled aggregated human IgG (AHIgG125I) (a polydispersed macromolecular protein biologically akin to immune complexes) in rats with ARF induced by either gentamicin or uranyl nitrate. AHIgG125I, 45 mg.per 100 gm of body weight, was administered intravenously to control and ARF rats; groups of five control and five ARF rats were sacrificed at 2, 4, 8, 16, and 24 hours after injection. AHIgG125I was measured in preparations of isolated glomeruli and compared with simultaneous liver, spleen, and blood levels. At all time intervals, blood levels of >7S AHIgG125I were similar in control and ARF rats. Mesangial uptake and disappearance of AHIgG125I were also similar in control rats and in rats with gentamicin or uranyl nitrate ARF. Inulin clearances were 1.05, 0.63, and 0.34 ml. per minute, and renal blood flows were 5.48, 4.68, and 5.32 ml. per minute in control, gentamicin, and uranyl nitrate rats, respectively. These studies demonstrate that the capillary lumen-mesangial passage of AHIgG125I was unimpeded in spite of major reductions in endothelial fenestral number and surface area known to occur in both models of nephrotoxic ARF. They further suggest (1) that plasmic flow through the mesangium is maintained, despite marked reductions in the formation of glomerular ultrafiltrate, (2) that the main route of access to the glomerular mesangium is in the region of the mesangial-endothelial interface at the edge of the mesangial zone, and (3) that the mesangial-endothelial interface zone may have different permeability characteristics than the peripheral capillary.

Original languageEnglish (US)
Pages (from-to)366-371
Number of pages6
JournalLaboratory Investigation
Volume45
Issue number4
StatePublished - Dec 1 1981

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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