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 ␣ (TNF-␣), 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-␣-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-␣ 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-␣-stimulated PMNs also resulted in significant increases (PϽ.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGFneutralizing 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.

Taurolidine inhibits the growth of a rat metastatic colorectal tumor cell line in vitro and in vivo and thus may have potential in the prevention of peritoneal metastases.

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ObjectiveTo evaluate the effect of inhalation of aerosolized opsonized dead Escherichia coli on inflammatory pulmonary neutrophil (PMN) apoptosis, lung injury, and survival in a PMN-mediated lung injury model in vivo. Summary Background DataNeutrophils that have transmigrated into an inflammatory focus display increased functional capacity and delayed apoptosis, resulting in an increased capacity to injure normal host tissue. The authors have previously shown that E. coli induces PMN apoptosis in vitro. MethodsLung injury mediated by PMNs was established by aortic occlusion and reperfusion. Adult male Sprague-Dawley rats were randomized into four groups: sham ischemia-reperfusion (I/R) treated with intratracheal inhalation of aerosolized normal saline, I/R treated with aerosolized normal saline intratracheally, I/R treated with aerosolized opsonized dead E. coli intratracheally, and I/R treated with aerosolized opsonized dead E. coli and the caspase inhibitor zVAD-FMK intratracheally 5 minutes before reperfusion. Both systemic and bronchoalveolar lavage PMNs were isolated and apoptosis was quantified at 0, 6, 12, 18, and 24 hours. Lung injury parameters including wet/dry lung weight ratio, histology, myeloperoxidase activity, and protein content were also assessed. In addition, a survival study was performed, both in a prophylactic and in a therapeutic setting.