Stromal-cell derived factor is expressed by dendritic cells and endothelium in human skin

Stromal-cell derived factor or SDF-1 is a CXC chemokine constitutively expr essed by stromal bone marrow cell cultures that binds to the G-protein-coup led receptor CXCR4, SDF-1/CXCR4 represents a unique, nonpromiscuous ligand/ receptor pair that plays an essential role in prenatal myelo- and lymphopoi esis as well as in cardiovascular and neural development. SDF-1 prevents en try of CXCR4-dependent (X4) HIV viruses in T lymphocytes, by binding and in ternalizing CXCR4. The expression pattern of SDF-1 protein in normal tissue s is not known. Here we describe an analysis of SDF-1 mRNA and protein in n ormal and inflamed skin by in situ hybridization and immunohistochemistry, using a novel anti-SI)F-l monoclonal antibody. We also describe the express ion pattern of CXCR4 receptor by immunohistochemistry. Our results show tha t SDF-1 protein and mRNA are normally expressed by endothelial cells, peric ytes, and either resident or explanted CD1a+ dendritic cells. Epithelial ce lls of sweat glands but not keratinocytes also express SDF-1. In various in flammatory skin diseases, a large number of mononuclear cells and fibroblas ts in close contact with CXCR4-positive lymphocytic infiltrates also expres s SDF-1. CXCR4 was also detected in many different normal cell types, inclu ding endothelial and epithelial cells, which points to a role for SDF-1/CXC R4 cell signaling in vascular and epithelial homeostasis, The demonstration of SDF-1 expression in dendritic and endothelial cells provides new insigh ts into the mechanisms of normal and pathological lymphocyte circulation an d makes it possible to envisage a role for locally secreted SDF-1 in the se lective incapacity of mucosal dendritic cells to support and propagate infe ction by X4 HIV isolates.