Hora K, Satriano J A, Santiago A, Mori T, Stanley E R, Shan Z, Schlondorff D
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1745-9. doi: 10.1073/pnas.89.5.1745.
The chemotactic factors responsible for complement-independent macrophage accumulation in immune-complex diseases such as glomerulonephritis remain unknown. Fc receptors for IgG complexes are found on mesangial cells of the kidney, which produce the macrophage growth factor colony-stimulating factor 1 (CSF-1). We therefore investigated the possible stimulation of mesangial-cell expression of CSF-1 and the recently identified monocyte-specific chemoattractant protein 1 (MCP-1) by IgG complexes. IgG complexes, but not monomeric IgG or F(ab')2 fragments of IgG, rapidly (2-8 h) increased mRNA for both CSF-1 (10-fold) and MCP-1 (20-fold) in cultured mouse mesangial cells. The increase of mRNA for CSF-1 and MCP-1 was not reduced by either cytochalasin B or D, indicating that Fc receptor occupancy is sufficient for signaling and that phagocytosis is not required to elicit this response. IgG complexes also caused a 10-fold increase in the secretion of CSF-1 and a 3- to 5-fold increase in secretion of MCP-1 into the cell culture medium. The synthesis and release of CSF-1 and MCP-1 by mesangial cells as a consequence of Fc receptor occupancy may be responsible for macrophage recruitment and activation at sites of immune-complex deposition.
在诸如肾小球肾炎等免疫复合物疾病中，负责非补体依赖性巨噬细胞积聚的趋化因子仍不清楚。在肾脏系膜细胞上发现了针对IgG复合物的Fc受体，系膜细胞可产生巨噬细胞生长因子集落刺激因子1（CSF-1）。因此，我们研究了IgG复合物对系膜细胞表达CSF-1以及最近发现的单核细胞特异性趋化蛋白1（MCP-1）的可能刺激作用。IgG复合物而非单体IgG或IgG的F(ab')2片段，能在培养的小鼠系膜细胞中迅速（2 - 8小时）增加CSF-1（10倍）和MCP-1（20倍）的mRNA水平。细胞松弛素B或D均未降低CSF-1和MCP-1的mRNA增加量，这表明Fc受体占据足以引发信号传导，且引发此反应无需吞噬作用。IgG复合物还使CSF-1的分泌增加了10倍，使MCP-1向细胞培养基中的分泌增加了3至5倍。由于Fc受体占据，系膜细胞合成和释放CSF-1及MCP-1可能是免疫复合物沉积部位巨噬细胞募集和激活的原因。
