CD73 mediates lymphocyte binding to vascular endothelium in inflamed human skin.
Inflammatory diseases of the skin are characterized by abundant lymphocytic infiltrates at the site of inflammation, which are critical for the perpetuation of chronic disease. Lymphocytes gain entry to the site of inflammation by the use of adhesion molecules, which recognize their counterparts on vascular endothelial cells. CD73 is a lymphocyte differentiation antigen, which has recently been shown to mediate lymphocyte binding to cultured endothelial cells. Here, we have examined its expression and function in inflammatory situations using inflammatory skin diseases as a model. In several idiopathic and allergic disorders of the skin, a vast majority of the skin-infiltrating lymphocytes were found to express CD73. However, on the circulating lymphocytes of these patients the expression of CD73 does not differ from that of healthy individuals. Of the peripheral blood lymphocytes (PBL) of patients, 13 % are CD73+; of these, 9 % express the cutaneous lymphocyte antigen (CLA), 32 % express CD45RO, and 86 % are L-selectin+. Only 1% of PBL express both CLA and CD73. In contrast, most skin-infiltrating lymphocytes express both molecules, which led us to investigate the role of CD73 in the skin-homing behavior of these cells. In the frozen-section adhesion assay, when PBL were treated with the anti-CD73 monoclonal antibody 4G4, their binding to the vascular endothelium in inflamed skin was inhibited by 70 %. Taken together, our results demonstrate that CD73+ lymphocytes preferentially accumulate into inflamed skin and, most importantly, that CD73 is involved in lymphocyte binding to vessels in inflamed skin. In the future, these findings may offer new means to treat inflammatory disorders of the skin.
Arvilommi
A M
AM
National Public Health Institute and MediCity Research Laboratories, University of Turku, Finland. annarv@utu.fi
Salmi
M
M
Airas
L
L
Kalimo
K
K
Jalkanen
S
S
D015720:5'-Nucleotidase / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D003872:Dermatitis / Q000276:immunology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D019041:L-Selectin / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D016131:Lymphocyte Subsets / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis; D012867:Skin / Q000276:immunology / Q000473:pathology
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D019041:L-Selectin; D017493:Leukocyte Common Antigens; D015720:5'-Nucleotidase