Braunstein S, Kaplan G, Gottlieb A B, Schwartz M, Walsh G, Abalos R M, Fajardo T T, Guido L S, Krueger J G
Laboratory of Investigative Dermatology, Rockefeller University, New York, New York 10021-6399.
J Invest Dermatol. 1994 Oct;103(4):601-4. doi: 10.1111/1523-1747.ep12396936.
Granulocyte/macrophage-colony-stimulating factor (GM-CSF), an immunomodulator of hematopoietic cells, has also been shown to stimulate human keratinocyte proliferation in vitro and speed healing of wounds in the skin of lepromatous leprosy patients. In this study we have examined the in vivo effects of recombinant human GM-CSF on epidermal keratinocyte proliferation and on expression of proteins marking regenerative epidermal growth. Skin biopsies from GM-CSF injected cutaneous sites were obtained between 1 and 6 d following administration of 7.5 or 15 micrograms of the growth factor. Activation of keratinocyte proliferation, quantified as the expression of the Ki67+ nuclear antigen, was noted 1 d following GM-CSF administration. A regenerative epidermal phenotype, demonstrated by immunohistochemical staining of cellular proteins involucrin, filaggrin, and keratin 16, was similarly noted as early as 1 d following GM-CSF injection. This phenotype persisted as late as 6 d post-injection. These results suggest that GM-CSF injection into human skin induces keratinocyte proliferation as well as regenerative differentiation of the epidermis. To date no other cytokine has been shown to be mitogenic for human keratinocytes both in vivo and in vitro or to alter keratinocyte differentiation along the "alternate" or regenerative pathway.
粒细胞/巨噬细胞集落刺激因子（GM-CSF）是造血细胞的一种免疫调节剂，已被证明在体外能刺激人角质形成细胞增殖，并加速瘤型麻风患者皮肤伤口的愈合。在本研究中，我们检测了重组人GM-CSF对表皮角质形成细胞增殖以及对标记再生性表皮生长的蛋白质表达的体内效应。在给予7.5微克或15微克生长因子后的1至6天内，从注射GM-CSF的皮肤部位获取皮肤活检组织。GM-CSF给药后1天，观察到角质形成细胞增殖的激活，以Ki67 +核抗原的表达进行量化。通过细胞蛋白内披蛋白、丝聚蛋白和角蛋白16的免疫组织化学染色证明的再生性表皮表型，同样在GM-CSF注射后1天就观察到。这种表型一直持续到注射后6天。这些结果表明，向人皮肤注射GM-CSF可诱导角质形成细胞增殖以及表皮的再生性分化。迄今为止，尚未有其他细胞因子被证明在体内和体外对人角质形成细胞具有促有丝分裂作用，或能沿着“替代”或再生途径改变角质形成细胞分化。
