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Effect of granulocyte macrophage‐colony stimulating factor on Langerhans cells in normal and healthy atopic subjects
Author(s) -
C. H. Smith,
Michael Allen,
Richard Groves,
Jonathan Barker
Publication year - 1998
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1046/j.1365-2133.1998.02360.x
Subject(s) - dermis , langerhans cell , granulocyte macrophage colony stimulating factor , epidermis (zoology) , intradermal injection , cell adhesion molecule , cytokine , immunology , dendritic cell , biology , medicine , pathology , antigen , anatomy
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 μg/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.