Effect of granulocyte macrophage-colony stimulating factor on Langerhans cells in normal and healthy atopic subjects.
Granulocyte macrophage-colony stimulating factor (GM-CSF) is a multipotent cytokine produced by many cutaneous cell types including keratinocytes. Langerhans cells (LC) represent the major antigen-presenting cells in skin, and in vitro studies demonstrate that GM-CSF is of pivotal importance in LC. Healthy volunteers (n = 3 non-atopic, n = 3 with atopy) received recombinant human GM-CSF (0. 05 microg/mL) by intradermal injection for 3 days to the same site. Diluent was injected in a similar manner as control. Biopsies were taken 24 h after the final injection and examined immunohistochemically for LC and inflammatory cell markers. Compared with control sites, intradermal GM-CSF resulted in shortening of dendritic cell processes and redistribution of LC in the epidermis; numbers of CD1a + cells in the epidermis were significantly decreased (P < 0.005), while those in the dermis were significantly increased (P < 0.05) following intradermal GM-CSF when compared with controls. Double labelling studies on epidermal CD1a + cells indicated de novo expression of intercellular adhesion molecule (ICAM)-1 and increased expression of HLA-DR following GM-CSF (P < 0. 005, P < 0.005, respectively). Additional findings included a marked mixed inflammatory cell infiltrate in the dermis and increased expression of the endothelial cell adhesion molecules E-selectin and ICAM-1. These data indicate that in normal human skin, GM-CSF induces changes in the phenotype and distribution of CD1a + cells consistent with LC functional maturation and exit from the epidermis to the dermis. As these events are central to the initiation of cutaneous inflammation, GM-CSF may potentially play a critical role in the pathogenesis of inflammatory dermatoses.
Skin Therapy Research Unit, St John's Institute of Dermatology, United Medical and Dental Schools, St Thomas' Hospital, London SE1 7EH, U.K.
C H
CH
Smith
M H
MH
Allen
R W
RW
Groves
J N
JN
Barker
D000293:Adolescent; D000328:Adult; D018949:Antigens, CD1 / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D019040:E-Selectin / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012867:Skin / Q000187:drug effects* / Q000276:immunology
D018949:Antigens, CD1; D019040:E-Selectin; D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor