Journal
BLOOD
Volume 124, Issue 24, Pages 3656-3665Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2014-04-572107
Keywords
-
Categories
Funding
- National Institutes of Health (National Institute of General Medical Sciences) [GM103441]
- National Heart, Lung, and Blood Institute [HL085607, HL093242, HL118676]
- Department of Defense [W81XWH-11-1-0226]
- Oklahoma Center for the Advancement of Science [HR13-160, HR13-020]
- National Natural Science Foundation of China [30928010, 31400692]
- Jiangsu Provincial Special Program of Medical Science [BL2012005]
- Jiangsu Province's Key Medical Center [ZX201102]
- American Heart Association [SDG7410022]
Ask authors/readers for more resources
O-glycosylation of podoplanin (PDPN) on lymphatic endothelial cells is critical for the separation of blood and lymphatic systems by interacting with platelet C-type lectin-like receptor 2 during development. However, how O-glycosylation controls endothelial PDPN function and expression remains unclear. In this study, we report that core 1 O-glycan-deficient or desialylated PDPN was highly susceptible to proteolytic degradation by various proteases, including metalloproteinases (MMP)-2/9. We found that the lymph contained activated MMP-2/9 and incubation of the lymph reduced surface levels of PDPN on core 1 O-glycan-deficient endothelial cells, but not on wild-type ECs. The lymph from mice with sepsis induced by cecal ligation and puncture, which contained bacteria-derived sialidase, reduced PDPN levels on wild-type ECs. The MMP inhibitor, GM6001, rescued these reductions. Additionally, GM6001 treatment rescued the reduction of PDPN level on lymphatic endothelial cells in mice lacking endothelial core 1 O-glycan or cecal ligation and puncture-treated mice. Furthermore, core 1 O-glycan-deficient or desialylated PDPN impaired platelet interaction under physiological flow. These data indicate that sialylated O-glycans of PDPN are essential for platelet adhesion and prevent PDPN from proteolytic degradation primarily mediated by MMPs in the lymph.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available