Heyworth C M, Pearson M A, Dexter T M, Wark G, Owen-Lynch P J, Whetton A D
Department of Experimental Haematology, Paterson Institute, Manchester, UK.
Growth Factors. 1995;12(3):165-72. doi: 10.3109/08977199509036876.
Macrophage Inflammatory Protein-1 alpha (MIP-1 alpha) can inhibit the proliferation of multipotent haemopoietic cells. Using the FDCP-Mix A4 multipotent stem cell line, MIP-1 alpha was shown to inhibit 1L-3 stimulated cell cycling (assessed using the [3H]-thymidine "suicide" assay). Furthermore, MIP-1 alpha can inhibit 1L-3-stimulated [3H]-thymidine incorporation in FDCP-Mix cells, with half maximal inhibition observed at 3 ng/ml MIP-1 alpha. Prostaglandin E2, but not MIP-1 alpha was able to elevate cyclic AMP levels in FDCP-Mix A4 cells although both agents can cause growth inhibition. However, MIP-1 alpha addition resulted in a pertussis-toxin-insensitive increase in the level of the second messenger inositol 1,4,5 triphosphate (Ins 1,4,5P3). This response was both rapid (maximal at 5 seconds) and transient. A half maximal effect was observed at 5 ng/ml MIP-1 alpha and the dose dependency correlated with that for MIP-1 alpha mediated growth inhibition. A rapid increase in cytosolic Ca2+ levels was also observed in response to MIP-1 alpha. Inositol lipid hydrolysis and an increase in cytosolic Ca2+ (signals normally associated with proliferation) may therefore be implicated in growth inhibitory mechanisms in multipotent cells.
巨噬细胞炎性蛋白-1α（MIP-1α）可抑制多能造血细胞的增殖。利用FDCP-Mix A4多能干细胞系，研究发现MIP-1α可抑制IL-3刺激的细胞周期进程（采用[3H]-胸腺嘧啶核苷“自杀”试验进行评估）。此外，MIP-1α可抑制IL-3刺激的FDCP-Mix细胞中[3H]-胸腺嘧啶核苷的掺入，在3 ng/ml MIP-1α时观察到半数最大抑制效应。前列腺素E2虽能引起生长抑制，但不能提高FDCP-Mix A4细胞中的环磷酸腺苷水平，而MIP-1α可以。然而，添加MIP-1α会导致第二信使肌醇1,4,5-三磷酸（Ins 1,4,5P3）水平出现百日咳毒素不敏感的升高。这种反应迅速（5秒时达到最大值）且短暂。在5 ng/ml MIP-1α时观察到半数最大效应，且剂量依赖性与MIP-1α介导的生长抑制相关。对MIP-1α的反应还观察到胞质Ca2+水平迅速升高。因此，肌醇脂质水解和胞质Ca2+增加（通常与增殖相关的信号）可能参与了多能细胞的生长抑制机制。
