Figure 2.

Systemic TGF-β1 blockade decreases tail lymphedema and improves lymphatic regeneration. A: Tail volume measurements in isotype control and TGFmab-treated animals (mean ± SEM; *P < 0.05). B: Representative photographs of isotype- (left) and TGFmab (right)-treated animals. Note improved wound repair, minimal edema, and lack of tail curvature indicative of fibrosis in TGFmab-treated animals as compared with controls. C: Representative microlymphangiography demonstrates flow of fluorescent-tagged large molecular weight dextran across the wound only in the TGFmab-treated animals. In contrast, isotype controls demonstrate pooling of fluorescence distal to the wound. D: Tc⁹⁹ lymphoscintigraphy demonstrating nearly ninefold greater lymphatic transport to lymph nodes at the base of the tail in TGFmab-treated mice as compared with isotype control (mean ± SEM; *P < 0.0001). Representative lymphoscintographs are presented (arrowhead: injection site near tip of tail; arrow: lymph node). E and F: Quantitation of podoplanin-positive lymphatic vessels demonstrates nearly twofold increase in number of vessels in tail tissues located distal to the zone of lymphatic disruption in mice treated with TGFmab as compared with isotype controls (mean ± SD; P < 0.0001). Representative 20× micrographs demonstrating scarce and dilated podoplanin positive vessels (arrow) in isotype-treated mice and abundant collapsed lymphatics (arrowheads) in TGFmab-treated mice. G and H: Quantitation of vWF-positive blood vessels (arrows), demonstrates a nonsignificant trend toward lower numbers of blood vessels in the TGFmab-treated animals.