Moore K J, Naito T, Martin C, Kelley V R
Immunogenetics and Transplantation, Renal Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
J Immunol. 1996 Jul 1;157(1):433-40.
Mice with the MRL background have a genetic propensity for autoimmune lupus nephritis. The lpr mutation on the MRL, but not the C3H background, induces rapid and fatal renal injury in which macrophages (M phi) are prominent. We previously established that CSF-1 accompanies M phi accumulation in the kidney of MRL-lpr mice. Furthermore, CSF-1 introduced into the kidney incites renal injury in mice with the lpr mutation, but not congenic strains. Notably, CSF-1 induces more severe tissue injury in MRL-lpr than in C3H-lpr mice. We hypothesized that M phi from the MRL background respond more readily to CSF-1 than normal strains. We establish herein the following: 1) glomerular M phi and bone marrow M phi (BMM phi) from MRL-lpr mice proliferate similarly to CSF-1; 2) MRL BMM phi proliferate more vigorously to CSF-1 than normal strains (C3H, BALB/c) or another strain with lpr (C3H-lpr); and 3) modulation of CSF-1 receptor expression by CSF-1 is more rapid in MRL than C3H BMM phi. We used a gene transfer strategy to deliver CSF-1 into the kidney to evaluate M phi response to CSF-1. We genetically modified tubular epithelial cells to produce CSF-1 (CSF-1-TECs) and placed these cells with BMM phi under the renal capsule. CSF-1-TEC + BMM phi caused a greater accumulation of M phi in the implant site and interstitium of MRL +/+ than C3H +/+ mice. Furthermore, CSF-1-TEC + BMM phi caused a lesion consisting of M phi in MRL +/+ mice, extending from the implant into the adjacent cortex. We suggest that the response of MRL M phi to CSF-1 is responsible for the notable accumulation of M phi in the MRL-lpr kidney.
具有MRL背景的小鼠具有自身免疫性狼疮性肾炎的遗传倾向。MRL背景上的lpr突变，而非C3H背景，会引发快速且致命的肾损伤，其中巨噬细胞（M phi）较为突出。我们之前证实，集落刺激因子-1（CSF-1）伴随M phi在MRL-lpr小鼠肾脏中的积聚。此外，将CSF-1导入肾脏会在具有lpr突变的小鼠中引发肾损伤，但在同基因品系中则不会。值得注意的是，CSF-1在MRL-lpr小鼠中诱导的组织损伤比在C3H-lpr小鼠中更严重。我们推测，来自MRL背景的M phi比正常品系对CSF-1的反应更迅速。我们在此证实了以下几点：1）来自MRL-lpr小鼠的肾小球M phi和骨髓M phi（BMM phi）对CSF-1的增殖反应相似；2）MRL BMM phi对CSF-1的增殖反应比正常品系（C3H、BALB/c）或另一个具有lpr的品系（C3H-lpr）更强烈；3）CSF-1对CSF-1受体表达的调节在MRL BMM phi中比在C3H BMM phi中更迅速。我们采用基因转移策略将CSF-1导入肾脏，以评估M phi对CSF-1的反应。我们对肾小管上皮细胞进行基因改造以产生CSF-1（CSF-1-TECs），并将这些细胞与BMM phi一起置于肾被膜下。与C3H +/+小鼠相比，CSF-1-TEC + BMM phi在MRL +/+小鼠的植入部位和间质中导致M phi的积聚更多。此外，CSF-1-TEC + BMM phi在MRL +/+小鼠中导致了由M phi组成的病变，从植入部位延伸至相邻皮质。我们认为，MRL M phi对CSF-1的反应是MRL-lpr肾脏中M phi显著积聚的原因。
