@article {1351160,
	title = {A novel pro-angiogenic function for interferon-γ-secreting natural killer cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {5},
	year = {2014},
	month = {2014 May 02},
	pages = {2885-92},
	abstract = {PURPOSE: To explore the function of natural killer (NK) cells in inflammatory angiogenesis in mice. METHODS: To study ocular angiogenic responses we used the cornea BFGF micropellet and the laser-induced choroidal neovascularization (CNV) mouse models (C57BL/6). To deplete NK cells in these models, we injected an anti-NK1.1 antibody or an isotype antibody as a control. Corneas or choroids were immunohistochemically stained for blood vessels (CD31), macrophages (F4/80), or CNV (isolectin-IB4). Vascular endothelial growth factors (VEGF), IFN-γ, or TNF-α levels were measured by real-time quantitative PCR (qPCR) or flow cytometry. A coculture assay of macrophages, NK cells, and human umbilical vein endothelial cells (HUVECs) was analyzed morphometrically to examine the ability of NK cells to induce angiogenesis in vitro. RESULTS: Our data demonstrate that in vivo depletion of NK cells leads to a significant reduction of corneal angiogenesis and CNV. Furthermore, NK cell depletion reduces macrophage infiltration into the cornea and mRNA expression levels of VEGF-A, VEGF-C, and VEGFR3 at day 7 after micropellet insertion. In the laser-induced CNV model, our data show that NK cell depletion leads to decreased areas of CNV and significantly reduced mRNA expression of VEGFs and IFN-γ in the choroid. An in vitro coculture assay shows an IFN-γ-dependent increase in VEGF expression levels, thereby increasing endothelial cell proliferation. CONCLUSIONS: Our findings demonstrate a novel pro-angiogenic function for NK cells, indicating that IFN-γ-secreting NK cells can induce angiogenesis by promoting enhanced VEGF expression by macrophages.},
	keywords = {Animals, Choroidal Neovascularization, Cornea, Disease Models, Animal, Immunohistochemistry, Interferon-gamma, Killer Cells, Natural, Macrophages, Mice, Mice, Inbred C57BL, Neovascularization, Pathologic, RNA, Messenger, Vascular Endothelial Growth Factors},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14093},
	author = {Lee, Hyun Soo and Schlereth, Simona L and Park, Eun Y and Emami-Naeini, Parisa and Chauhan, Sunil K and Dana, Reza}
}
