Neutrophil-derived MMP-9 and heparanase modulate VEGF-A bioavailability and bioactivity to promote lymphangiogenesis. (A) Footpad skin whole mounts were examined for lymphatic vessels at 14 days postimmunization after administration of complete or treated CM into immunized, NIMP-R14-treated mice. (B) Lymphatic vessel density in footpad skin whole mounts after administration of complete or treated CM into immunized, NIMP-R14-treated mice. (C) Footpad sections were immunostained for VEGFA:VEGFR2 complexes in footpads. (D) Mean fluorescence intensity of VEGF-A:VEGFR2 complexes in footpads from immunized, NIMP-R14-treated mice receiving complete or treated CM. (E) Footpad sections were examined at higher magnification for localization of VEGF-A:VEGFR2 complexes with lymphatic vessels. (F) Footpad swelling after administration of complete or treated CM into immunized, NIMP-R14-treated mice. Images from panels A, C, and F are representative of 5 mice per treatment group (n = 5). Scale bar in panels A and F represent 75 μm and 2 mm, respectively. Scale bars in panels C and E represent 75 and 50 μm, respectively. Data from panels B and D are pooled from 5 mice per treatment group (n = 5), and bars represent mean ± SD. *P < .05; **P < .01.