Systemic blockade of VEGFR-1/flt-1 and VEGFR-2/flk-1 inhibits skin inflammation and lymphatic enlargement. Differential immunofluorescence stains for CD31 (red) and LYVE-1 (green) in mouse ear skin 24 hours after antigen challenge. Edema formation and enlargement of lymphatic vessels was not significantly influenced by systemic application of rat control IgG (A), antibodies against VEGFR-1/flt-1 (B), or antibodies against VEGFR-2/flk-1 (C). Scale bar, 100 μm. In mice that were treated with a combination of antibodies against VEGFR-1/flt-1 and VEGFR-2/flk-1, edema formation and enlargement of lymphatic vessels was significantly reduced (D). Ear swelling is expressed as the increase over the original ear thickness in micrometers (E). Computer-assisted morphometric analysis of LYVE-1–stained vessels 24 hours after challenge revealed a significant reduction in lymphatic vessel size in mice that were treated with antibodies against VEGFR-1/flt-1 and VEGFR-2/flk-1 (F). Significantly reduced numbers of CD11b⁺ macrophages in the oxazolone-challenged ears after systemic blockade of VEGFR-1/flt-1 (G). Data are expressed as mean plus or minus SEM (n = 3). *P < .01; **P < .001.