Platelet interaction with lymphatics aggravates intestinal inflammation by suppressing lymphangiogenesis
Hirokazu Sato, Masaaki Higashiyama, Hideaki Hozumi, Shingo Sato, Hirotaka Furuhashi, Takeshi Takajo, Koji Maruta, Yuichi Yasutake, Kazuyuki Narimatsu, Kenichi Yoshikawa, Chie Kurihara, Yoshikiyo Okada
(+6 others)
2016
American Journal of Physiology - Gastrointestinal and Liver Physiology
failure is a histopathological feature of inflammatory bowel disease (IBD). Recent studies show that interaction between platelets and podoplanin on lymphatic endothelial cells (LECs) suppresses lymphangiogenesis. We aimed to investigate the role of platelets in the inflammatory process of colitis, which is likely to be through modulation of lymphangiogenesis. Lymphangiogenesis in colonic mucosal specimens from patients with IBD was investigated by studying mRNA expression of lymphangiogenic
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... tors and histologically by examining lymphatic vessel (LV) densities. Involvement of lymphangiogenesis in intestinal inflammation was studied by administering VEGF-receptor 3 (VEGF-R3) inhibitors to the mouse model of colitis using dextran sulfate sodium and evaluating platelet migration to LVs. The inhibitory effect of platelets on lymphangiogenesis was investigated in vivo by administering antiplatelet antibody to the colitis mouse model and in vitro by coculturing platelets with lymphatic endothelial cells. Although mRNA expressions of lymphangiogenic factors such as VEGF-R3 and podoplanin were significantly increased in the inflamed mucosa of patients with IBD compared with those with quiescent mucosa, there was no difference in LV density between them. In the colitis model, VEGF-R3 inhibition resulted in aggravated colitis, decreased lymphatic density, and increased platelet migration to LVs. Administration of an antiplatelet antibody increased LV densities and significantly ameliorated colitis. Coculture with platelets inhibited proliferation of LECs in vitro. Our data suggest that despite elevated lymphangiogenic factors during colonic inflammation, platelet migration to LVs resulted in suppressed lymphangiogenesis, leading to aggravation of colitis by blocking the clearance of inflammatory cells. Modulating the interaction between platelets and LVs could be a new therapeutic means for treating IBD. lymphangiogenesis; platelet; lymphatic vessels; podoplanin; inflammatory bowel disease THE MAJOR ROLE OF LYMPHATICS is to drain interstitial fluid and transport immune cells to the lymph nodes. Blocking lymphangiogenesis by inhibiting VEGF-receptor 3 (VEGF-R3) signaling resulted in aggravation of murine colitis (23). Enhancing lymphangiogenesis through the VEGF-C/VEGF-R3 pathway reduces murine colitis (13). These findings suggest that
doi:10.1152/ajpgi.00455.2015
pmid:27313177
fatcat:tgsd7zpcgnbuhjtoc5aksqeyu4
