Enhanced natural-killer cell and erythropoietic activities in VEGF-A-overexpressing mice delay F-MuLU-induced erythroleukemia
Enhanced natural-killer cell and erythropoietic activities in VEGF-A-overexpressing mice delay F-MuLU-induced erythroleukemia
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DOI：
10.1182/blood-2005-11-026823
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发表时间：
2007-03-01
期刊：
影响因子：
20.3
通讯作者：
Ben-David, Yaacov
中科院分区：
文献类型：
--
作者：
Cervi, David;Shaked, Yuval;Ben-David, Yaacov
We have previously reported that VEGF-A, in combination with MCP-5, contributes to leukemia progression within the splenic microenvironment of mice infected with F-MuLV. To study the influence of constitutively elevated VEGF-A levels on the progression of erythroleukemia, mice heterozygous for a VEGF-A "hypermorphic" allele (Vegf(hi/+)) were inoculated with F-MuLV. Unexpectedly, a significant delay in erythroleukemia was observed in Vegf(hi/+) mice when compared with wildtype controls. These results suggested an altered physiologic response arising from elevated VEGF-A levels that decelerated erythroleukemic progression. Characterization of hematopoiesis in Vegf(hi/+) spleens showed a higher natural killer cell activity, elevated B cells, and a decrease in T-cell number. Furthermore, higher erythroid progenitors (ie, CD34(+), CD36(+), and Teri119(+) cells) were evident in the bone marrow, spleen, and peripheral blood of Vegf(hi/+) mice. The CFU-E levels were significantly elevated in Vegf(hi/+) bone marrow cultures, and this elevation was blocked by a neutralizing antibody to VEGF-A receptor (VEGFR-2). Moreover, erythroleukemic mice were treated with recombinant erythropoietin and, similar to diseased Vegf(hi/+) mice, showed a delay in disease progression. We propose that a compensatory erythropoietic response combined with increased natural killer (NK) cell activity account for the extended. survival of erythroleukemic, Vegf(hi/+) mice.
