Intraglomerular and interstitial leukocyte infiltration, adhesion molecules, and interleukin-1 alpha expression in 15 cases of antineutrophil cytoplasmic autoantibody-associated renal vasculitis

Am J Kidney Dis. 1996 Jan;27(1):48-57. doi: 10.1016/s0272-6386(96)90030-x.


In renal biopsy specimens from 15 patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated renal vasculitis, the infiltrating intraglomerular and interstitial leukocytes were localized and the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the cytokine interleukin-1 alpha (IL-1 alpha) were studied by an immunohistochemical method. Intraglomerular leukocytes were mainly macrophages (13.46 +/- 9.29 cells/glomerular cross-section) and, to a lesser extent, T lymphocytes (4.61 +/- 2.81 cells/glomerular cross-section). Staining with VCAM-1, which was negative in the undamaged tufts, was strongly positive in necrotizing-extracapillary lesions. Staining with ICAM-1 was also present in the damaged tufts, but its pattern was more diffuse. Intraglomerular IL-1 alpha was found in all biopsy specimens. Where the Bowman's capsule was not damaged, the periglomerular infiltrating cells were macrophages (42.6 +/- 25.2 cells/glomerular cross-section) and T lymphocytes (51.06 +/- 33.0 cells/glomerular cross-section). When there was a granulomatous lesion involving the glomerulus, the number of cells per granulomatous area revealed a massive number of CD45-positive leukocytes (345.83 +/- 237.47 cells/granulomatous lesion), many of them positive for activity markers (HLA-DR, IL-2R), adhesion molecules, and IL-1 alpha. Many activated cells were also present in interstitial areas of perivascular clusters of leukocytes, in which T lymphocytes (prevalently CD4+ cells) outnumbered the macrophages (331.55 +/- 207.85 cells/0.05 mm2 area v 125.68 +/- 60.57 cells/0.05 mm2 area). Adhesion molecules and IL-1 alpha were found in both tubular and vascular areas in all biopsy specimens. Our data strongly support the involvement of both the adhesion molecules ICAM-1 and VCAM-1 in the recruitment of intraglomerular leukocytes in renal vasculitis, indicate that VCAM-1 is a very good marker of necrotizing-extracapillary damage, and suggest its crucial connection with the macrophage recruitment in these vasculitic lesions. The presence of histochemically detectable levels of IL-1 alpha in glomeruli, tubules, and vessels and on some inflammatory cells supports its involvement in the vasculitic lesions, probably by triggering a positive feedback that increases the damage.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antineutrophil Cytoplasmic
  • Autoantibodies / biosynthesis*
  • Biomarkers
  • Cell Movement
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Interleukin-1 / biosynthesis*
  • Kidney Glomerulus* / blood supply
  • Kidney Glomerulus* / pathology
  • Leukocytes / pathology*
  • Male
  • Middle Aged
  • Vascular Cell Adhesion Molecule-1 / biosynthesis*
  • Vasculitis / immunology*
  • Vasculitis / metabolism


  • Antibodies, Antineutrophil Cytoplasmic
  • Autoantibodies
  • Biomarkers
  • Interleukin-1
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1