Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

Hdl Handle:
http://hdl.handle.net/10147/209138
Title:
Proinflammatory mediators stimulate neutrophil-directed angiogenesis.
Authors:
McCourt, M; Wang, J H; Sookhai, S; Redmond, H P
Affiliation:
Department of Surgery, Professorial Unit, Cork University Hospital, Ireland.
Citation:
Arch Surg. 1999 Dec;134(12):1325-31; discussion 1331-2.
Journal:
Archives of surgery (Chicago, Ill. : 1960)
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209138
PubMed ID:
10593330
Abstract:
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 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.
Language:
eng
MeSH:
Antigens, CD95/physiology; Cells, Cultured; Endothelial Growth Factors/physiology; Endothelium, Vascular/*immunology; Humans; Inflammation Mediators/*physiology; Interleukin-6/physiology; Lipopolysaccharides/immunology; Lymphokines/physiology; Neovascularization, Pathologic/*immunology; Neutrophils/*immunology; Tumor Necrosis Factor-alpha/physiology; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
ISSN:
0004-0010 (Print); 0004-0010 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMcCourt, Men_GB
dc.contributor.authorWang, J Hen_GB
dc.contributor.authorSookhai, Sen_GB
dc.contributor.authorRedmond, H Pen_GB
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.en_GB
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-

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.