Thromboxane (TX) is an arachidonic acid metabolite that exerts its actions through a TX-prostanoid (TP) receptor, which is a G-protein-coupled receptor with seven transmembrane domains. In the present study, we investigated the role of TP signaling in facilitating lymphangiogenesis during inflammation.
Inflammation was induced by repeated intraperitoneal injections of lipopolysaccharide (LPS), and lymphangiogenesis was induced in the diaphragm in a time-dependent manner. Compared with WT mice, LPS-induced lymphangiogenesis in TP^-/- mouse diaphragm tissue was suppressed, and this was accompanied by reduced drainage from the peritoneal cavity. TP-positive macrophages and T cells accumulated in the diaphragm and produced VEGF-C/D in a TP-dependent manner. Removal of macrophages and T cells resulted in reduced lymphangiogenesis and lower levels of VEGF-C/D expression. Moreover, TP^-/- bone marrow chimeric mice exhibited reduced lymphangiogenesis. TP knockout specific to macrophages and T cells also led to reduced lymphangiogenesis and drainage function in mice with LPS injections. The present results suggest that TP signaling exerts pro-lymphangiogenic activity by acting on macrophages and T cells accumulated during inflammation, and that TP signaling represents a novel target for controlling lymphangiogenesis.