03705nas a2200517   4500000000100000008004100001260001600042653001500058653001000073653001200083653001400095653001500109653002100124653001100145653005300156653001100209653002800220653002900248653001800277653002100295653002400316653002500340653001500365653000900380653002500389653001600414653002500430653000900455653001700464653001800481100001300499700001200512700001400524700001100538700001800549700001500567700001300582700001500595700001600610700001300626245018900639300001200828490000800840520232500848022001403173       1992                            d  c1992 Jun 0110aAdolescent10aAdult10aAnimals10aCHO Cells10aCricetinae10aEscherichia coli10aFemale10aGranulocyte-Macrophage Colony-Stimulating Factor10aHumans10aInjections, Intradermal10aInjections, Subcutaneous10aKeratinocytes10aLangerhans Cells10aLeprosy, Borderline10aLeprosy, lepromatous10aLeukocytes10aMale10aMicroscopy, Electron10aMiddle Aged10aRecombinant Proteins10aSkin10aTime Factors10aWound Healing1 aKaplan G1 aWalsh G1 aGuido L S1 aMeyn P1 aBurkhardt R A1 aAbalos R M1 aBarker J1 aFrindt P A1 aFajardo T T1 aCelona R00aNovel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing.  a1717-280 v1753 a<p>Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that rGM-CSF, when introduced into the skin, leads to enhanced keratinocyte growth, the selective recruitment of Langerhans cells into the dermis, and enhanced wound healing of the prepared site. There was no evidence of an enhanced cell-mediated response to Mycobacterium leprae, and bacillary numbers remained unchanged.</p>  a0022-1007