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Scientific article
English

Polymorphonuclear leukocytes play a key role in the generation of "wire-loop" lesions induced by a murine IgG3 rheumatoid factor

Published inKidney international, vol. 49, no. 3, p. 647-655
Publication date1996
Abstract

Murine IgG3 anti-IgG2a rheumatoid factor (RF) monoclonal antibodies (mAb) with cryoglobulin activity are able to induce skin leukocytoclastic vasculitis and glomerulonephritis resembling "wire-loop" glomerular lesions in normal mice. Since polymorphonuclear leukocyte (PMN) infiltration is one of the major pathological changes observed in both types of lesions, we determined the role of PMN and complement in the generation of these two different lesions, induced by 6-19 IgG3 RF mAb, by interfering with adhesion molecules known for their involvement of PMN-endothelial cell interaction or by depleting mice of their PMN or C3. Our results have demonstrated that first, the PMN-endothelial cell interaction mediated by leukocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) was crucial for the generation of 6-19 RF mAb-induced skin leukocytoclastic vasculitis, but not for glomerular lesions; second, PMN played an active role in the development of "wire-loop" glomerular lesions; in the absence of the PMN glomerular infiltration, 6-19 RF mAb induced a different type of glomerular lesions, characterized by voluminous intracapillary thrombi and mesangial deposits, but not subendothelial deposits; and third, the activation of the complement system did not appear to play a major role in both skin and glomerular lesions.

Keywords
  • Animals
  • Antibodies, Monoclonal
  • Glomerulonephritis/immunology/pathology/ prevention & control
  • Immunoglobulin G/ immunology
  • Intercellular Adhesion Molecule-1/immunology
  • Lymphocyte Function-Associated Antigen-1/immunology
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron
  • Neutrophils/ immunology/pathology
  • Rheumatoid Factor/ toxicity
  • Skin/ blood supply/drug effects
  • Vasculitis/immunology/pathology/ prevention & control
Citation (ISO format)
FULPIUS, Thierry et al. Polymorphonuclear leukocytes play a key role in the generation of ‘wire-loop’ lesions induced by a murine IgG3 rheumatoid factor. In: Kidney international, 1996, vol. 49, n° 3, p. 647–655. doi: 10.1038/ki.1996.93
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ISSN of the journal0085-2538
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