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 expressed by stromal bone marrow cell cultures that binds to the G-protein-coupled receptor CXCR4. SDF-1/CXCR4 represents a unique, nonpromiscuous ligand/receptor pair that plays an essential role in prenatal myelo- and lymphopoiesis as well as in cardiovascular and neural development. SDF-1 prevents entry of CXCR4-dependent (X4) HIV viruses in T lymphocytes, by binding and internalizing CXCR4. The expression pattern of SDF-1 protein in normal tissues is not known. Here we describe an analysis of SDF-1 mRNA and protein in normal and inflamed skin by in situ hybridization and immunohistochemistry, using a novel anti-SDF-1 monoclonal antibody. We also describe the expression pattern of CXCR4 receptor by immunohistochemistry. Our results show that SDF-1 protein and mRNA are normally expressed by endothelial cells, pericytes, and either resident or explanted CD1a+ dendritic cells. Epithelial cells of sweat glands but not keratinocytes also express SDF-1. In various inflammatory skin diseases, a large number of mononuclear cells and fibroblasts in close contact with CXCR4-positive lymphocytic infiltrates also express SDF-1. CXCR4 was also detected in many different normal cell types, including endothelial and epithelial cells, which points to a role for SDF-1/CXCR4 cell signaling in vascular and epithelial homeostasis. The demonstration of SDF-1 expression in dendritic and endothelial cells provides new insights into the mechanisms of normal and pathological lymphocyte circulation and makes it possible to envisage a role for locally secreted SDF-1 in the selective incapacity of mucosal dendritic cells to support and propagate infection by X4 HIV isolates.
Pablos
J L
JL
Servicio de Reumatología, Centro de Investigación, Hospital 12 de Octubre, Madrid, Spain. jipablos@h12o.es
Amara
A
A
Bouloc
A
A
Santiago
B
B
Caruz
A
A
Galindo
M
M
Delaunay
T
T
Virelizier
J L
JL
Arenzana-Seisdedos
F
F
D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008833:Microcirculation; D018613:Microscopy, Confocal; D020286:Pericytes / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D012867:Skin / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4