Activated human neutrophils release hepatocyte growth factor/scatter factor.

Hdl Handle:
http://hdl.handle.net/10147/209076
Title:
Activated human neutrophils release hepatocyte growth factor/scatter factor.
Authors:
McCourt, M; Wang, J H; Sookhai, S; Redmond, H P
Affiliation:
Department of Surgery, Professorial Unit, Cork University Hospital, Cork,, Ireland.
Citation:
Eur J Surg Oncol. 2001 Jun;27(4):396-403.
Journal:
European journal of surgical oncology : the journal of the European Society of, Surgical Oncology and the British Association of Surgical Oncology
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209076
DOI:
10.1053/ejso.2001.1133
PubMed ID:
11417987
Abstract:
BACKGROUND: Hepatocyte growth factor or scatter factor (HGF/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+/-216, 484+/-221 and 565+/-278 pg/ml, respectively) compared to controls (118+/-42 pg/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.
Language:
eng
MeSH:
Analysis of Variance; Blotting, Western; Cell Adhesion Molecules/*metabolism; Endothelial Growth Factors/*metabolism; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gene Expression Regulation/drug effects; Hepatocyte Growth Factor/*metabolism; Humans; Interleukin-8/pharmacology; Lipopolysaccharides/pharmacology; Lymphocyte Activation/drug effects; Lymphokines/*metabolism; N-Formylmethionine Leucyl-Phenylalanine/pharmacology; Neovascularization, Pathologic; Neutrophils/*drug effects/*secretion; Tumor Necrosis Factor-alpha/pharmacology; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
ISSN:
0748-7983 (Print); 0748-7983 (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.accessioned2012-02-03T15:11:37Z-
dc.date.available2012-02-03T15:11:37Z-
dc.date.issued2012-02-03T15:11:37Z-
dc.identifier.citationEur J Surg Oncol. 2001 Jun;27(4):396-403.en_GB
dc.identifier.issn0748-7983 (Print)en_GB
dc.identifier.issn0748-7983 (Linking)en_GB
dc.identifier.pmid11417987en_GB
dc.identifier.doi10.1053/ejso.2001.1133en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209076-
dc.description.abstractBACKGROUND: Hepatocyte growth factor or scatter factor (HGF/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+/-216, 484+/-221 and 565+/-278 pg/ml, respectively) compared to controls (118+/-42 pg/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.en_GB
dc.language.isoengen_GB
dc.subject.meshAnalysis of Varianceen_GB
dc.subject.meshBlotting, Westernen_GB
dc.subject.meshCell Adhesion Molecules/*metabolismen_GB
dc.subject.meshEndothelial Growth Factors/*metabolismen_GB
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_GB
dc.subject.meshFlow Cytometryen_GB
dc.subject.meshGene Expression Regulation/drug effectsen_GB
dc.subject.meshHepatocyte Growth Factor/*metabolismen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInterleukin-8/pharmacologyen_GB
dc.subject.meshLipopolysaccharides/pharmacologyen_GB
dc.subject.meshLymphocyte Activation/drug effectsen_GB
dc.subject.meshLymphokines/*metabolismen_GB
dc.subject.meshN-Formylmethionine Leucyl-Phenylalanine/pharmacologyen_GB
dc.subject.meshNeovascularization, Pathologicen_GB
dc.subject.meshNeutrophils/*drug effects/*secretionen_GB
dc.subject.meshTumor Necrosis Factor-alpha/pharmacologyen_GB
dc.subject.meshVascular Endothelial Growth Factor Aen_GB
dc.subject.meshVascular Endothelial Growth Factorsen_GB
dc.titleActivated human neutrophils release hepatocyte growth factor/scatter factor.en_GB
dc.contributor.departmentDepartment of Surgery, Professorial Unit, Cork University Hospital, Cork,, Ireland.en_GB
dc.identifier.journalEuropean journal of surgical oncology : the journal of the European Society of, Surgical Oncology and the British Association of Surgical Oncologyen_GB
dc.description.provinceMunster-
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