Hulkower K, Brosnan C F, Aquino D A, Cammer W, Kulshrestha S, Guida M P, Rapoport D A, Berman J W
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
J Immunol. 1993 Mar 15;150(6):2525-33.
We have examined the expression of factors associated with the growth, differentiation, and chemotaxis of cells of the monocyte/macrophage series in the central nervous system of Lewis rats sensitized to develop experimental allergic encephalomyelitis. CSF-1 mRNA increased significantly over that found in control animals (sensitized with OVA in CFA or CFA alone). The elevation in the levels of this growth factor commenced immediately before the onset of early clinical signs and peaked immediately before maximal clinical incidence of disease. Expression of CSF-1 message declined to base-line values with resolution of the disease process. CSF-1 protein was also detected in the central nervous system at the height of clinical disease. Expression of the receptor for CSF-1, the proto-oncogene c-fms, also paralleled the early disease process. Elevated levels of c-fms mRNA were detected immediately before the onset and peaked at the height of clinical signs of disease. In contrast to CSF-1 levels, elevated c-fms message expression persisted after resolution of the acute phase of experimental allergic encephalomyelitis. Levels of macrophage chemotactic factor-1 message were also elevated immediately before the onset of clinical signs, peaked with the height of clinical disease, and declined with resolution of the disease. Unlike CSF-1 or c-fms, no endogenous macrophage chemotactic factor-1 message was detected in control animals. Macrophage chemotactic factor-1 protein was demonstrated by Western blot in the central nervous system at the height of clinical disease. The results support the conclusion that expression of factors that specifically target cells of the monocyte/macrophage series are an important component of the disease process in experimental allergic encephalomyelitis.
我们检测了致敏以诱发实验性变应性脑脊髓炎的Lewis大鼠中枢神经系统中与单核细胞/巨噬细胞系细胞生长、分化和趋化性相关因子的表达。与对照动物（用卵清蛋白在弗氏完全佐剂中致敏或仅用弗氏完全佐剂致敏）相比，集落刺激因子-1（CSF-1）mRNA显著增加。这种生长因子水平的升高在早期临床症状出现前即刻开始，并在疾病临床发病率最高之前达到峰值。随着疾病进程的缓解，CSF-1信息的表达降至基线值。在临床疾病高峰期，中枢神经系统中也检测到了CSF-1蛋白。CSF-1受体（原癌基因c-fms）的表达也与早期疾病进程平行。在疾病症状出现前即刻检测到c-fms mRNA水平升高，并在疾病临床症状高峰期达到峰值。与CSF-1水平不同，实验性变应性脑脊髓炎急性期缓解后，c-fms信息表达仍持续升高。巨噬细胞趋化因子-1信息水平在临床症状出现前即刻也升高，在临床疾病高峰期达到峰值，并随着疾病的缓解而下降。与CSF-1或c-fms不同，对照动物中未检测到内源性巨噬细胞趋化因子-1信息。在临床疾病高峰期，通过蛋白质印迹法在中枢神经系统中证实了巨噬细胞趋化因子-1蛋白的存在。这些结果支持以下结论：特异性靶向单核细胞/巨噬细胞系细胞的因子表达是实验性变应性脑脊髓炎疾病进程的重要组成部分。
