Avraham-Davidi, Inbal and Yona, Simon and Grunewald, Myriam and Landsman, Limor and Cochain, Clement and Silvestre, Jean Sebastien and Mizrahi, Haim and Faroja, Mohammad and Strauss-Ayali, Dalit and Mack, Matthias and Jung, Steffen and Keshet, Eli (2013) On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells. JOURNAL OF EXPERIMENTAL MEDICINE, 210 (12). pp. 2611-2625. ISSN 0022-1007, 1540-9538
Full text not available from this repository. (Request a copy)Abstract
Adult neovascularization relies on the recruitment of monocytes to the target organ or tumor and functioning therein as a paracrine accessory. The exact origins of the recruited monocytes and the mechanisms underlying their plasticity remain unclear. Using a VEGF-based transgenic system in which genetically tagged monocytes are conditionally summoned to the liver as part of a VEGF-initiated angiogenic program, we show that these recruited cells are derived from the abundant pool of circulating Ly6C(hi) monocytes. Remarkably, however, upon arrival at the VEGF-induced organ, but not the naive organ, monocytes undergo multiple phenotypic and functional changes, endowing them with enhanced proangiogenic capabilities and, importantly, with a markedly increased capacity to remodel existing small vessels into larger conduits. Notably, monocytes do not differentiate into long-lived macrophages, but rather appear as transient accessory cells. Results from transfers of presorted subpopulations and a novel tandem transfer strategy ruled out selective recruitment of a dedicated preexisting subpopulation or onsite selection, thereby reinforcing active reprogramming as the underlying mechanism for improved performance. Collectively, this study uncovered a novel function of VEGF, namely, on-site education of recruited "standard" monocytes to become angiogenic and arteriogenic professional cells, a finding that may also lend itself for a better design of angiogenic therapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ADULT NEOVASCULARIZATION; TUMOR REFRACTORINESS; ENDOTHELIAL-CELLS; BLOOD MONOCYTES; GENE-EXPRESSION; MACROPHAGES; SUBSETS; GROWTH; MICE; PROGRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Mar 2020 08:14 |
| Last Modified: | 26 Mar 2020 08:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15666 |
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