title: Adhesion of leukocytes to dermal endothelial cells is induced after single-dose, but reduced after repeated doses of UVA.
abstract: Approximately 20-50% of ultraviolet A (UVA) irradiation delivered to the skin surface may reach the human dermal microvascular endothelial cells (HDMEC) that play a pivotal role in cellular inflammatory tissue; however, the pathophysiologic role of HDMEC in UVA-induced skin changes is largely unknown. Based on previous in vivo and in vitro studies revealing UVA-induced expression of endothelial adhesion molecules, we studied isolated HDMEC under various conditions in order to further delineate the impact of UVA on these cells. The expression of cell adhesion molecules was determined by flow cytometry and the resulting changes of stable adhesion of leukocytes to endothelial cells were quantitated for granulocytes, lymphocytes, and monocytes using a newly developed multicellular adhesion assay. Additionally, antibody blocking experiments were performed to delineate the role of individual cell adhesion molecules in UVA-induced leukocyte adherence. High-dose polychromatic UVA (25 J per cm2, maximal emission at 375 nm) induced intercellular adhesion molecule-1 and E-selectin with different kinetics but correlating the adhesion of leukocyte subsets. This effect subsided, however, in the course of 3-6 daily applied UVA doses. Moreover, pro-inflammatory cytokine challenge by tumor necrosis factor-alpha and interleukin-1-alpha resulted in significantly weaker induction of intercellular adhesion molecule-1 and E-selectin in repeatedly UVA-exposed HDMEC. Differential quantitation of peripheral blood derived granulocytes, lymphocytes, and monocytes revealed reduced adhesion particularly of lymphocytes followed by monocytes and granulocytes compared with leukocyte adhesion to nonirradiated but cytokine-stimulated HDMEC. It is concluded that UVA substantially influences endothelial cell adhesion molecules expression and thus directly interferes with leukocyte adhesion to endothelial cells. Divergent UVA-induced effects in this respect can be attributed to the mode of UV exposure as well as to the condition of endothelial cells prior to UVA exposure.
authors.affiliation: Department of Dermatology, Ludwig-Maximilians University, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Heckmann
authors.forename: M
authors.initials: M
authors.lastname: Pirthauer
authors.forename: G
authors.initials: G
authors.lastname: Plewig
mesh_terms: D002448:Cell Adhesion / Q000528:radiation effects; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007962:Leukocytes / Q000502:physiology / Q000528:radiation effects*; D012867:Skin / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1