Parkinson E K, Graham G J, Daubersies P, Burns J E, Heufler C, Plumb M, Schuler G, Pragnell I B
CRC Beatson Laboratories, Beatson Institute for Cancer Research, Bearsden, Glasgow, U.K.
J Invest Dermatol. 1993 Aug;101(2):113-7. doi: 10.1111/1523-1747.ep12363603.
The maintenance and regulation of continuously renewing tissues is ultimately controlled at the level of stem-cell proliferation. We have recently identified a reversible inhibitor of hemopoietic stem-cell proliferation (stem-cell inhibitor [SCI]), which is identical to the macrophage inflammatory protein, MIP-1 alpha, a 69-amino-acid heparin-binding cytokine. To test the cell/tissue specificity of the inhibition of proliferation by SCI/MIP-1 alpha, we have investigated its activity on epidermal keratinocytes, the principal cell type of another continuously renewing tissue. Here we show that SCI/MIP-1 alpha inhibits the proliferation of epidermal keratinocytes in vitro and that the MIP-1 alpha mRNA is present in epidermal Langerhans cells but not in keratinocytes. This suggests an important growth regulatory function for SCI/MIP-1 alpha in keratopoiesis, as well as hemopoiesis, and may also indicate a novel role for the epidermal Langerhans cell. As SCI/MIP-1 alpha can inhibit the proliferation of embryologically distinct precursor cells, this raises the possibility that it may also function in a number of other tissues.
持续更新组织的维持与调控最终是在干细胞增殖水平上进行控制的。我们最近鉴定出一种造血干细胞增殖的可逆抑制剂(干细胞抑制剂 [SCI]),它与巨噬细胞炎性蛋白MIP-1α 相同,MIP-1α 是一种含69个氨基酸的肝素结合细胞因子。为了测试SCI/MIP-1α 对增殖抑制的细胞/组织特异性,我们研究了其对表皮角质形成细胞的活性,表皮角质形成细胞是另一种持续更新组织的主要细胞类型。在此我们表明,SCI/MIP-1α 在体外抑制表皮角质形成细胞的增殖,并且MIP-1α mRNA存在于表皮朗格汉斯细胞中,而不存在于角质形成细胞中。这表明SCI/MIP-1α 在角质形成以及造血过程中具有重要的生长调节功能,也可能暗示表皮朗格汉斯细胞具有新的作用。由于SCI/MIP-1α 能够抑制胚胎学上不同的前体细胞的增殖,这增加了它也可能在许多其他组织中发挥作用的可能性。