Expression and modulation of the vitronectin receptor on human dermal microvascular endothelial cells.
Microvascular endothelial cells express a variety of cell-surface integrins in vivo and in vitro with varying affinities for matrix proteins. The vitronectin receptor (VnR), a complex of the alpha v and beta 3 integrin chains, is capable of binding to a variety of matrix proteins that are deposited in injured tissues, including vitronectin, fibrinogen, and thrombin. Staining of frozen sections of human skin with antibodies recognizing the VnR and examination by immunofluorescence microscopy demonstrates staining in a vascular pattern suggesting in vivo expression of the vitronectin receptor on endothelial cells. Examination of pure cultures of human dermal microvascular endothelial cells (HDMEC) by flow-cytometric analysis and enzyme-linked immunosorbent assay confirmed that HDMEC also express cell surface VnR complex in vitro. Stimulation of human dermal microvascular endothelial cells in vitro with agents that stimulate protein kinase C resulted in dose- and time-dependent increases in expression of alpha v and beta 3 integrin chains. Additionally, stimulation with basic fibroblast growth factor induced similar increases, but stimulation with transforming growth factor-beta or interleukin-1 alpha failed to increase VnR expression. Increases in cell-surface VnR expression also correlated with an increased ability of microvascular endothelial cells to bind to vitronectin, but not fibronectin-coated surfaces. Although increases in cell-surface expression of beta 3 paralleled increases in expression of cell-surface alpha v, regulation of mRNA expression was distinct for each chain. These data suggests that microvascular endothelial cells express the VnR complex in vivo, that the cell-surface expression of this integrin on dermal microvascular endothelial cells can be regulated, and that this regulation may be important in cell adherence, cell migration, and wound healing.
D015152:Blotting, Northern; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005434:Flow Cytometry; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000378:metabolism; D008856:Microscopy, Fluorescence; D011493:Protein Kinase C / Q000502:physiology; D016024:Receptors, Cytoadhesin / Q000737:chemistry / Q000502:physiology*; D019030:Receptors, Vitronectin
D016207:Cytokines; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D011493:Protein Kinase C