02338nas a2200373   4500000000100000008004100001260001300042653002500055653001800080653005300098653001100151653001600162653002900178653001800207653001200225653002500237653001700262653000900279653003300288100001700321700001300338700001700351700001500368700001200383700001500395700001600410700001400426700001600440245011600456300001000572490000800582520136000590022001401950       1994                            d  c1994 Oct10aCell Differentiation10aCell Division10aGranulocyte-Macrophage Colony-Stimulating Factor10aHumans10aHypertrophy10aInjections, Subcutaneous10aKeratinocytes10aleprosy10aRecombinant Proteins10aRegeneration10aSkin10aSkin Physiological Phenomena1 aBraunstein S1 aKaplan G1 aGottlieb A B1 aSchwartz M1 aWalsh G1 aAbalos R M1 aFajardo T T1 aGuido L S1 aKrueger J G00aGM-CSF activates regenerative epidermal growth and stimulates keratinocyte proliferation in human skin in vivo.  a601-40 v1033 a<p>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.</p>  a0022-202X