Search

Vascular endothelial growth factor A (VEGF-A) is upregulated during hypoxia and is the major regulator of angiogenesis. VEGF-A expression has also been found to recruit myeloid cells to ischemic tissues where they contribute to angiogenesis. This study investigates the mechanisms underlying neutrophil recruitment to VEGF-A as well as the characteristics of these neutrophils. A previously undefined circulating subset of neutrophils shown to be CD49d(+)VEGFR1(high)CXCR4(high) was identified in mice and humans. By using chimeric mice with impaired VEGF receptor 1 (VEGFR1) or VEGFR2 signaling (Flt-1tk(-/-), tsad(-/-)), we found that parallel activation of VEGFR1 on neutrophils and VEGFR2 on endothelial cells was required for VEGF-A-induced recruitment of circulating neutrophils to tissue. Intravital microscopy of mouse microcirculation revealed that neutrophil recruitment by VEGF-A versus by the chemokine macrophage inflammatory protein 2 (MIP-2 [CXCL2]) involved the same steps of the recruitment cascade but that an additional neutrophil integrin (eg, VLA-4 [CD49d/CD29]) played a crucial role in neutrophil crawling and emigration to VEGF-A. Isolated CD49d(+) neutrophils featured increased chemokinesis but not chemotaxis compared with CD49d(-) neutrophils in the presence of VEGF-A. Finally, by targeting the integrin α4 subunit (CD49d) in a transplantation-based angiogenesis model that used avascular pancreatic islets transplanted to striated muscle, we demonstrated that inhibiting the recruitment of circulating proangiogenic neutrophils to hypoxic tissue impairs vessel neoformation. Thus, angiogenesis can be modulated by targeting cell-surface receptors specifically involved in VEGF-A-dependent recruitment of proangiogenic neutrophils without compromising recruitment of the neutrophil population involved in the immune response to pathogens., (© 2015 by The American Society of Hematology.)

Production of biomass adapted to the degradation of a mixture of chlorobenzene (CB) and 1,2-dichlorobenzene (DCB) was investigated in a batch culture with substrates supplied by pulses. CB and o-DCB concentrations which gave the best adapted biomass productivity were determined and found to be 150 and 30 microl l(-1), respectively. The biomass productivity was 51 mg l(-1) h(-1). The biomass yield was 0.38 g of biomass dry weight per gram of substrate. The pulses of 200 microl CB and 40 microl o-DCB, were inhibitory to the bacterial culture. Among the metabolites, muconic acid was found in large quantities in the medium and in the cells. At a time between two pulses of 60 min, adding 150 microl CB and 30 microl o-DCB per each pulse, 7.6g l(-1) of biomass was obtained. The produced biomass served as an inoculum for the biotrickling filter which treated industrial waste gases contaminated by CBs. The method of adapted biomass production was described using CBs, but the degradation of any other toxic volatile pollutant can be improved using this technique.