Show simple item record

dc.contributor.authorMcCourt, M
dc.contributor.authorWang, J H
dc.contributor.authorSookhai, S
dc.contributor.authorRedmond, H P
dc.date.accessioned2012-02-03T15:13:16Z
dc.date.available2012-02-03T15:13:16Z
dc.date.issued2012-02-03T15:13:16Z
dc.identifier.citationArch Surg. 1999 Dec;134(12):1325-31; discussion 1331-2.en_GB
dc.identifier.issn0004-0010 (Print)en_GB
dc.identifier.issn0004-0010 (Linking)en_GB
dc.identifier.pmid10593330en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209138
dc.description.abstractBACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+/-49 and 484+/-80 pg/mL, respectively; for all, presented as mean +/- SEM) compared with control experiments (32+/-4 pg/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome, wound healing, and tumor growth.
dc.language.isoengen_GB
dc.subject.meshAntigens, CD95/physiologyen_GB
dc.subject.meshCells, Cultureden_GB
dc.subject.meshEndothelial Growth Factors/physiologyen_GB
dc.subject.meshEndothelium, Vascular/*immunologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInflammation Mediators/*physiologyen_GB
dc.subject.meshInterleukin-6/physiologyen_GB
dc.subject.meshLipopolysaccharides/immunologyen_GB
dc.subject.meshLymphokines/physiologyen_GB
dc.subject.meshNeovascularization, Pathologic/*immunologyen_GB
dc.subject.meshNeutrophils/*immunologyen_GB
dc.subject.meshTumor Necrosis Factor-alpha/physiologyen_GB
dc.subject.meshVascular Endothelial Growth Factor Aen_GB
dc.subject.meshVascular Endothelial Growth Factorsen_GB
dc.titleProinflammatory mediators stimulate neutrophil-directed angiogenesis.en_GB
dc.contributor.departmentDepartment of Surgery, Professorial Unit, Cork University Hospital, Ireland.en_GB
dc.identifier.journalArchives of surgery (Chicago, Ill. : 1960)en_GB
dc.description.provinceMunster
html.description.abstractBACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+/-49 and 484+/-80 pg/mL, respectively; for all, presented as mean +/- SEM) compared with control experiments (32+/-4 pg/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome, wound healing, and tumor growth.


This item appears in the following Collection(s)

Show simple item record