Immune complex-degradation ability of macrophages in MRL/Mp-lpr/lpr lupus mice and its regulation by cytokines.
Impaired clearance of circulating and/or deposited immune complexes (IC) by the mononuclear phagocytic system is one of the major factors in the pathogenesis of IC diseases. MRL/Mp-lpr/lpr (MRL/lpr) lupus mice spontaneously develop a lethal glomerulonephritis associated with IC deposition. The ability of macrophages to degrade phagocytozed IC and regulation of this degradation in MRL/lpr mice were examined. In 4-month-old MRL/lpr mice, macrophages accumulated in the affected glomeruli and these macrophages contained many phagosomes containing electron-dense bodies. When culture supernatant of human T cell line HUT102 was administered intraperitoneally into disease-bearing MRL/lpr mice, degradation of these electron-dense bodies in the macrophages in glomeruli was noted. We developed a quantitative in vitro assay for IC degradation activity of MRL/lpr resident peritoneal macrophages (RPM) using peroxidase-labelled IC derived from MRL/lpr mouse sera. The ability of the RPM to degrade IC was remarkably enhanced by the pretreatment with HUT102 cell products and the related human recombinant cytokines, lymphotoxin and IL-1 alpha. Moreover, pretreatment of RPM from non-diseased MRL/Mp-+/+ mice with the culture supernatant of spleen cells from diseased MRL/lpr mice reduced their IC degradation activity. These results suggested that the ability of macrophages to degrade IC in MRL/Mp strains of mice is under the regulation of cytokines, and the impaired ability in the disease-bearing mice may be the result of abnormalities in the cytokine system in these mice.
Kanno
H
H
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Tachiwaki
O
O
Nose
M
M
Kyogoku
M
M
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007105:Immune Complex Diseases / Q000209:etiology; D007678:Kidney Glomerulus / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice
D000936:Antigen-Antibody Complex; D016207:Cytokines