Proinflammatory Mediators Stimulate Neutrophil-Directed Angiogenesis

摘要: Background Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating process angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. Hypothesis The acute inflammatory response stimulus for PMN-directed angiogenesis. Methods were isolated from healthy volunteers stimulated with lipopolysaccharide (LPS), tumor necrosis α (TNF-α), interleukin 6 (IL-6), anti-human Fas monoclonal antibody. Culture supernatants assayed VEGF using enzyme-linked immunosorbent assays. LPS- TNF-α–stimulated PMNs then added human umbilical vein cells microvessel assessed cell proliferation 5-bromodeoxyuridine labeling. Tubule formation was also on MATRIGEL basement membrane matrix. lysed measure total release, expression detected Western blot analysis. Results Lipopolysaccharide TNF-α stimulation resulted significantly increased release PMN (532 ± 49 484 80 pg/mL, respectively; all, presented as mean SEM) compared control experiments (32 4 pg/mL). Interleukin had no effect. significant increases (P Conclusion Activated are directly angiogenic by releasing VEGF, this has important implications inflammation, capillary leak syndrome, wound healing, growth.