Immune complex-degradation ability of macrophages in MRL/Mp-lpr/lpr lupus mice and its regulation by cytokines

H. Kanno, O. Tachiwaki, M. Nose, M. Kyogoku

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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 electrondense 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-1α. 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.

Original languageEnglish
Pages (from-to)115-121
Number of pages7
JournalClinical and Experimental Immunology
Volume95
Issue number1
DOIs
Publication statusPublished - 1994

Keywords

  • IL- 1
  • glomerulonephritis
  • immune complex disease
  • lymphotoxin
  • phagolysosome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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