LOCAL EXTRAHEPATIC EXPRESSION OF COMPLEMENT GENES C-3, FACTOR-B, C2, AND C-4 IS INCREASED IN MURINE LUPUS NEPHRITIS
LOCAL EXTRAHEPATIC EXPRESSION OF COMPLEMENT GENES C-3, FACTOR-B, C2, AND C-4 IS INCREASED IN MURINE LUPUS NEPHRITIS
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DOI：
10.1172/jci113780
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发表时间：
1988-11-01
影响因子：
15.9
通讯作者：
COLTEN, HR
中科院分区：
文献类型：
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作者：
PASSWELL, J;SCHREINER, GF;COLTEN, HR
系统性红斑狼疮（SLE）与受影响器官中补体蛋白和免疫复合物的存在有关。由于补体蛋白在肝和肝外部位合成，我们研究了SLE小鼠模型，以确定局部和体液（肝脏）补体合成的相对重要性。肾脏中C3、C4和C2 mRNA的增加与MRL lpr/lpr小鼠（一种自发发展SLE的品系）中肾炎的发展一致。两种因子B信使RNA转录物在肾脏和肠道中表达; SLE肾炎与长因子B mRNA的减少和短因子mRNA的增加有关。局部C3和B蛋白合成的增加以及伴随的肾小球和肾间质巨噬细胞浸润抑制了（lpr/lpr）小鼠中mRNA含量的增加。除肾脏外，与MRL（+/+）动物相比，在（lpr/lpr）动物的肺、心脏和肠中观察到C3、C4、C2和因子B mRNA增加，在肝脏中的增加程度较小。这些结果表明，在SLE局部补体基因的表达发挥了作用，在慢性肾小球肾炎和其他器官的自身免疫性动脉炎的发病机制。
Systemic lupus erythematosus (SLE) is associated with the presence of complement proteins and immune complexes in affected organs. Since complement proteins are synthesized in hepatic and extrahepatic sites, we studied a murine model of SLE to ascertain the relative importance of local and humoral (liver) synthesis of complement. C3, C4, and C2 mRNA increase in kidney coincident with the development of nephritis in the MRL lpr/lpr mouse, a strain that spontaneously develops SLE. Two factor B messenger RNA transcripts are expressed in kidney and intestine; SLE nephritis is associated with decrease in the long factor B mRNA and increase in the short form. Increased local synthesis of C3 and B protein and a concomitant glomerular and renal interstitial macrophage infiltrate paralleled the increase in mRNA content in the (lpr/lpr) mice. In addition to kidney, an increase in C3, C4, C2 and factor B mRNA was noted in the lung, heart and intestine and to a lesser extent in liver of (lpr/lpr) in comparison to the MRL (+/+) animals. These results suggest that in SLE local expression of complement genes plays a role in the pathogenesis of chronic glomerulonephritis and in the autoimmune arteritis of other organs.