POLYMORPHONUCLEAR LEUKOCYTES PLAY A KEY ROLE IN THE GENERATION OF WIRE-LOOP LESIONS INDUCED BY A MURINE IGG3 RHEUMATOID-FACTOR

Murine IgG3 anti-IgG2a rheumatoid factor (RF) monoclonal antibodies (m Ab) with cryoglobulin activity are able to induce skin leukocytoclasti c vasculitis and glomerulonephritis resembling ''wire-loop'' glomerula r lesions in normal mice. Since polymorphonuclear leukocyte (PMN) infi ltration is one of the major pathological changes observed in both typ es of lesions, we determined the role of PMN and complement in the gen eration of these two different lesions, induced by 6-19 IgG3 RF mAb, b y interfering with adhesion molecules known for their involvement of P MN-endothelial cell interaction or by depleting mice of their PMN or C 3. 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 g eneration 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, t he activation of the complement system did not appear to play a major role in both skin and glomerular lesions.