Infiltration of COX-2–expressing macrophages is a prerequisite for IL-1β–induced neovascularization and tumor growth
J. Clin. Invest. Shintaro Nakao, et al. 115:2979 doi:10.1172/JCI23298 [Go to this article.]

Figure 1
IL-1β– and VEGF-induced angiogenesis and inflammatory cell infiltration in mouse corneas. (A) Neovascularization 6 days after implanting Hydron pellets containing human or mouse IL-1β or mouse VEGF at the doses shown into male BALB/c mouse corneas. hIL-1β, human IL-1β; mIL-1β, mouse IL-1β; mVEGF, mouse VEGF. (B) Corneal neovascularization induced by human IL-1β (30 ng) or mouse VEGF (200 ng) at the indicated time points. (C) Quantitative analysis of neovascularization on days 4 (white bars) and 6 (black bars). Areas are expressed in mm². Bars show the mean ± SD of independent experiments (n = 6 or 7). (D) Corneas implanted with IL-1β or VEGF stained by H&E at the indicated time points. (E) Corneal sections on days 2 or 6 after IL-1β–pellet implantation, labeled immunohistochemically (brown) for Gr-1, which was detected in infiltrating cells on days 2 and 6, and F4/80, which was detected on day 6. (F) FACS analysis of infiltrating cells from IL-1β– or VEGF-implanted corneas (n = 5) at the indicated times. Cells were stained with PE-CD11b mAb and FITC–Gr-1 or FITC-F4/80 mAb. The percentages of infiltrating CD11b⁺Gr-1⁺ cells in IL-1β–implanted corneas were 53.5% ± 10.4% (day 2), 15.8% ± 4.9% (day 4), and 3.15% ± 0.27% (day 6). The percentages of infiltrating CD11b⁺Gr-1⁺ cells in VEGF-implanted corneas were 2.99% ± 1.37% (day 2), 1.95% ± 0.75% (day 4), and 1.08% ± 0.74% (day 6). The percentages of infiltrating CD11b⁺F4/80⁺ cells in IL-1β–implanted corneas were 1.85% ± 1.28% (day 2), 5.56% ± 1.61% (day 4), and 5.52% ± 1.14% (day 6). The percentages of infiltrating CD11b⁺F4/80⁺ cells in VEGF-implanted corneas were 0.81% ± 0.47% (day 2), 1.30% ± 1.03% (day 4), and 1.90% ± 0.98% (day 6).