COLONY-STIMULATING FACTOR-I IN THE INDUCTION OF LUPUS NEPHRITIS

COLONY-STIMULATING FACTOR-I IN THE INDUCTION OF LUPUS NEPHRITIS
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DOI:
10.1038/ki.1993.141
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发表时间:
1993-05-01
影响因子:
19.6
通讯作者:
KELLEY, VR
KELLEY, VR
中科院分区:
医学1区
文献类型:
--
作者:
BLOOM, RD;FLORQUIN, S;KELLEY, VR

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在这项研究中,我们研究了集落刺激因子-1(CSF-1)在狼疮性肾炎的诱导中的作用。本研究旨在探讨自身免疫性狼疮性肾炎小鼠肾小球巨噬细胞(Mphi)大量涌入与脑脊液-1(CSF-1)的关系。用原位杂交法检测MRL-LPR小鼠在肾损伤前(12周龄)和肾损伤后(12周龄)肾组织中CSF-1的转录本。4周龄时,肾小球内可检测到CSF-1mRNA,且随疾病严重程度的加重而增加。为了检测肾小球Mphi是否需要CSF-1,我们从MRL-LPR小鼠的肾脏中分离出Mphi。分离出两种类型的Glom Mphi(具有与有无蛋白尿相关的形态和生长特征)。在无CSF-1的培养条件下,来自蛋白尿小鼠的Glom Mphi的活性保持不变,来自蛋白尿前期小鼠的Glom Mphi不能存活,在培养液中中和CSF-1降低了蛋白尿前Glom Mphi的活性(5-6倍),而蛋白尿Glom Mphi的活性降低了<1,5 X。此外,补充CSF-1诱导了蛋白尿前Glom Mphi的10倍于无CSF-1的培养液。相反,蛋白尿GLOM MPHI对CSF-1的反应没有增殖。这些研究表明,CSF-1诱导肾小球内巨噬细胞的增殖和分化,进而导致肾脏损伤。
In this study we examine the role of colony stimulating factor-1 (CSF-1) in the induction of lupus nephritis. The purpose of the study was to establish the relationship of CSF-1 to the prominent influx of macrophages (Mphi) in the glomeruli of MRL-lpr mice with autoimmune lupus nephritis. The kidneys of MRL-lpr mice were examined before (< 12 weeks of age) and after (>12 weeks of age) renal injury for CSF-1 transcripts by in situ hybridization. CSF-1 mRNA was detected at four weeks of age within glomeruli and increased with disease severity. To examine whether glomerular Mphi (glom Mphi) required CSF-1 we isolated Mphi from the kidneys of MRL-lpr mice. Two types of glom Mphi (with morphological and growth characteristics which correlated with the presence or absence of proteinuria) were isolated. Under CSF-1-free culture conditions, where the viability of glom Mphi from proteinuric mice was maintained, glom Mphi from pre-proteinuric mice were unable to survive, Neutralization of CSF-1 in the media reduced viability of pre-proteinuric glom Mphi (5 to 6 X), while viability of proteinuric glom Mphi was diminished < 1,5 X. Additionally, CSF-1 supplementation induced a 10 x proliferation of pre-proteinuric glom Mphi when compared to CSF-1-free medium. In contrast, proteinuric glom Mphi did not proliferate in response to CSF-1. These studies suggest that CSF-1 induces macrophage proliferation and differentiation within glomeruli and, in turn, renal injury.