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

Fulpius, Thierry
Pastore, Yves
Published in Kidney International. 1996, vol. 49, no. 3, p. 647-655
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 AnimalsAntibodies, MonoclonalGlomerulonephritis/immunology/pathology/ prevention & controlImmunoglobulin G/ immunologyIntercellular Adhesion Molecule-1/immunologyLymphocyte Function-Associated Antigen-1/immunologyMiceMice, Inbred BALB CMicroscopy, ElectronNeutrophils/ immunology/pathologyRheumatoid Factor/ toxicitySkin/ blood supply/drug effectsVasculitis/immunology/pathology/ prevention & control
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Other version: http://www.nature.com/ki/journal/v49/n3/pdf/ki199693a.pdf
PMID: 8648905
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