T lymphocyte adhesion mechanisms within inflamed human kidney: studies with a Stamper-Woodruff assay

Am J Pathol. 1999 Feb;154(2):503-14. doi: 10.1016/S0002-9440(10)65296-0.

Abstract

Renal inflammatory conditions are characterized by mononuclear cell recruitment to sites of inflammation. We have developed a modified Stamper-Woodruff assay system to analyze mechanisms of functional T cell adhesion to cryostat sections of renal biopsy material from patients with vasculitic glomerulonephritis (GN) and acute allograft rejection. Peripheral blood T cells adhered to intraglomerular, periglomerular, and tubulointerstitial regions of the cortex. Blocking monoclonal antibodies against tissue expressed ICAM-1, VCAM-1, and the CS-1 domain of fibronectin (CS-1Fn) differentially attenuated T cell adhesion. Glomerular adhesion in vasculitic GN and tubulointerstitial adhesion in acute rejection were particularly sensitive to both anti-ICAM-1 and anti-VCAM-1 antibodies, indicating a prominent role for ICAM-1 and VCAM-1 at glomerular sites in vasculitis and at tubulointerstitial sites in rejection. Furthermore, using KL/4 cells (LFA-1 expressing) and Jurkat cells (VLA-4 expressing), we demonstrated specific LFA-1/ICAM-1- and VLA-4/VCAM-1-mediated interactions within glomerular and tubulointerstitial compartments. Jurkat cells also adhered to VCAM-1-free sites, and binding was inhibitable by anti-CS-1Fn antibody, thereby demonstrating a role for VLA-4/fibronectin interactions especially at intraglomerular sites in acute rejection where VCAM-1 is notably absent. We therefore propose a prominent functional role for ICAM-1, VCAM-1, and CS-1 domain fibronectin in T cell recruitment to the inflamed kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Antibodies, Blocking / immunology
  • Antibodies, Monoclonal / immunology
  • Cell Adhesion
  • Cell Count
  • Glomerulonephritis / immunology
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Graft Rejection / immunology
  • Graft Rejection / metabolism*
  • Graft Rejection / pathology
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Jurkat Cells / metabolism
  • K562 Cells / metabolism
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Peptides / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • Up-Regulation
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vasculitis / immunology
  • Vasculitis / metabolism*
  • Vasculitis / pathology

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Vascular Cell Adhesion Molecule-1
  • CS1 peptide
  • Intercellular Adhesion Molecule-1