Activated human neutrophils release hepatocyte growth factor/scatter factor.
AffiliationDepartment of Surgery, Professorial Unit, Cork University Hospital, Cork,, Ireland.
MeSHAnalysis of Variance
Cell Adhesion Molecules/*metabolism
Endothelial Growth Factors/*metabolism
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation/drug effects
Hepatocyte Growth Factor/*metabolism
Lymphocyte Activation/drug effects
Tumor Necrosis Factor-alpha/pharmacology
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
MetadataShow full item record
CitationEur J Surg Oncol. 2001 Jun;27(4):396-403.
JournalEuropean journal of surgical oncology : the journal of the European Society of, Surgical Oncology and the British Association of Surgical Oncology
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.
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