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PSGL-1 regulates platelet P-selectin-mediated endothelial activation and shedding of P-selectin from activated platelets.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Dole, Vandana S. Bergmeier, Wolfgang Patten, Ian S. Hirahashi, Junichi Mayadas, Tanya N. Wagner, Denisa D. |
| Copyright Year | 2007 |
| Abstract | We have previously shown that activated platelets in circulation stimulate release of endothelial Weibel-Palade bodies thus increasing leukocyte rolling in venules. P-selectin on the activated platelets mediates adhesion to leukocytes via PSGL-1 and is rapidly shed into plasma. We were interested in studying the role of PSGL-1 in regulating expression and function of platelet P-selectin. We show here that PSGL-1 is critical for the activation of endothelial cells in venules of mice infused with activated platelets. The interaction of platelet P-selectin with PSGL-1 is also required for P-selectin shedding, as P-selectin was retained significantly longer on the surface of activated platelets infused into PSGL-1(-/-) compared to wild-type mice. The leukocyte integrin alphaMbeta2 (Mac-1) was not required for P-selectin shedding. In addition to shedding, P-selectin can be downregulated from the platelet surface through internalization and this is the predominant mechanism in the absence of PSGL-1. We demonstrate that leukocyte-neutrophil elastase, known to cleave P-selectin in vitro, is not the major sheddase for P-selectin in vivo. In conclusion, interaction of platelet P-selectin with PSGL-1 is crucial for activation of the endothelium andWeibel-Palade body secretion. The interaction with PSGL-1 also results in rapid shedding of P-selectin thus downregulating the inflammatory potential of the platelet. |
| File Format | PDF HTM / HTML |
| DOI | 10.1160/TH07-03-0207 |
| PubMed reference number | 17938805 |
| Journal | Medline |
| Volume Number | 98 |
| Issue Number | 4 |
| Alternate Webpage(s) | https://th.schattauer.de/en/contents/archive/issue/741/manuscript/8712/download.html |
| Alternate Webpage(s) | https://doi.org/10.1160/TH07-03-0207 |
| Journal | Thrombosis and haemostasis |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
