Kanno H, Tachiwaki O, Nose M, Kyogoku M
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Clin Exp Immunol. 1994 Jan;95(1):115-21. doi: 10.1111/j.1365-2249.1994.tb06024.x.
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.
单核吞噬细胞系统对循环和/或沉积的免疫复合物（IC）清除功能受损是IC疾病发病机制的主要因素之一。MRL/Mp-lpr/lpr（MRL/lpr）狼疮小鼠会自发发展出与IC沉积相关的致命性肾小球肾炎。我们研究了MRL/lpr小鼠中巨噬细胞降解吞噬的IC的能力以及这种降解的调节机制。在4月龄的MRL/lpr小鼠中，巨噬细胞在受影响的肾小球中积聚，并且这些巨噬细胞含有许多包含电子致密体的吞噬体。当将人T细胞系HUT102的培养上清液腹腔注射到患病的MRL/lpr小鼠中时，观察到肾小球中巨噬细胞内这些电子致密体的降解。我们利用源自MRL/lpr小鼠血清的过氧化物酶标记的IC开发了一种定量体外测定MRL/lpr常驻腹膜巨噬细胞（RPM）IC降解活性的方法。用HUT102细胞产物以及相关的人重组细胞因子、淋巴毒素和IL-1α预处理后，RPM降解IC的能力显著增强。此外，用患病的MRL/lpr小鼠脾细胞的培养上清液预处理未患病的MRL/Mp-+/+小鼠的RPM会降低其IC降解活性。这些结果表明，小鼠MRL/Mp品系中巨噬细胞降解IC的能力受细胞因子调节，患病小鼠中这种能力受损可能是这些小鼠细胞因子系统异常的结果。
