Growth factor regulation of neutrophil-endothelial cell interactions.
The effects of the angiogenic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on human polymorphonuclear leukocyte (PMNL)-endothelial cell adhesion and transendothelial migration (TEM) were investigated. Stimulation of human umbilical vein endothelial cells by VEGF or bFGF for 18 h up-regulated intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 expression and significantly increased PMNL adhesion and TEM in response to complement fragment 5a (C5a) or interleukin (IL)-8. In contrast, continued exposure to bFGF (24 h-6 days) down-regulated basal and IL-1- or tumor necrosis factor (TNF)-induced intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin expression as well as PMNL adhesion and TEM. These effects could be reversed by introduction of high concentrations of TNF-alpha, C5a, or IL-8. None of these inhibitory effects was observed with VEGF. The acute effects of bFGF and VEGF may facilitate PMNL emigration during acute inflammation, but continued bFGF production may have anti-inflammatory actions during chronic inflammation, angiogenesis, and tumor defense by inhibition of endothelial activation for leukocyte recruitment.
Zhang
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Departments of Pediatrics, Microbiology and Immunology, and Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
Issekutz
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AC
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015815:Cell Adhesion Molecules; D016228:Endothelial Growth Factors; D006133:Growth Substances; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2