Downregulation of lymphatic vessel formation factors in PGF_{2 alpha} -induced luteolysis in the cow.

摘要

Prostaglandin F_{2 alpha} (PGF_{2 alpha} ) induces luteolysis in cows and causes infiltration of immune cells, which resembles inflammatory immune response. Since the general immune response is mediated by the lymphatic system, we hypothesized that luteolysis is associated with generation of an immune response that involves lymphatic vessels in the bovine corpus luteum (CL). The CL was obtained from Holstein cows at the mid-luteal phase (days 10-12, ovulation=day 0) by ovariectomy at various time points after PGF_{2 alpha} injection. Lymphatic endothelial cell (LyEC) marker, endothelial hyaluronan receptor 1 (LYVE1), levels decreased significantly 12 h after PGF_{2 alpha} injection. Podoplanin, another LyEC marker, decreased from 15 min after PGF_{2 alpha} injection. PGF_{2 alpha} also diminished mRNA expression of lymphangiogenic factors, such as vascular endothelial growth factor (VEGF) C, VEGFD and VEGF receptor 3 (VEGFR3). During PGF_{2 alpha} -induced luteolysis, the levels of mRNA expression of tumor necrosis factor alpha (TNF alpha ; the major pro-inflammatory cytokine) and chemokine (C-X-C motif) ligand 1 (neutrophil chemokine) were increased. On the other hand, chemokine (C-C motif) ligand 21, which regulates outflow of immune cells from tissues via the lymphatic vessels during an immune response, was decreased. This study demonstrated that the lymphatic network in the CL is disrupted during luteolysis and suggests that during luteolysis, immune cells can induce a local immune response in the CL without using the lymphatic vessels.