The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Proinflammatory Mediators Stimulate Neutrophil-Directed Angiogenesis
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.
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Cites
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Interleukin 6 Induces the Expression of Vascular Endothelial Growth Factor
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Vascular permeability factor (VPF, VEGF) in tumor biology
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Cited by
Templeton, A. J., McNamara, M. G., Šeruga, B., Vera-Badillo, F. E., Aneja, P., Ocaña, A., Leibowitz-Amit, R., Sonpavde, G., Knox, J. J., Tran, B., et al. (2014) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/dju124 · Cited by 2,829
The role of myeloid cells in the promotion of tumour angiogenesis
Murdoch, C., Muthana, M., Coffelt, S. B., & Lewis, C. E. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2444 · Cited by 1,642
Developmental and Pathological Angiogenesis
Chung, A. S., & Ferrara, N. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154002 · Cited by 722
Templeton, A. J., Ace, O., McNamara, M. G., Al-Mubarak, M., Vera-Badillo, F. E., Hermanns, T., Šeruga, B., Ocaña, A., Tannock, I. F., & Amir, E. (2014) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-14-0146 · Cited by 719
Pathophysiology of Inflammatory Bowel Disease: Innate Immune System
Saez, A., Herrero-Fernandez, B., Gomez-Bris, R., Sánchez-Martinez, H., & Gonzalez-Granado, J. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021526 · Cited by 580
Metadata
- Authors
- McCourt, M.
- Venue
- Archives of Surgery
- Publisher
- American Medical Association (AMA)
- Published
- 1999-12-01
- Volume
- 134
- Issue
- 12
- Pages
- 1325
- ISSN
- 0004-0010 (ISSN-L)
- OpenAlex
- W1991500417
- Cited by
- 268
- References
- 28
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- closed
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