Claire S. Whyte
Exposure of plasminogen and a novel plasminogen receptor, Plg-RKT, on activated human and murine platelets.
Whyte, Claire S.; Morrow, Gael B.; Baik, Nagyung; Booth, Nuala A.; Jalal, Mohammed M.; Parmer, Robert J.; Miles, Lindsey A.; Mutch, Nicola J.
Authors
Dr Gael Morrow g.morrow1@rgu.ac.uk
Chancellor's Fellow
Nagyung Baik
Nuala A. Booth
Mohammed M. Jalal
Robert J. Parmer
Lindsey A. Miles
Nicola J. Mutch
Abstract
Plasminogen activation rates are enhanced by cell surface binding. We previously demonstrated that exogenous plasminogen binds to phosphatidylserine-exposing and spread platelets. Platelets contain plasminogen in their α-granules, but secretion of plasminogen from platelets has not been studied. Recently, a novel transmembrane lysine-dependent plasminogen receptor, Plg-RKT, has been described on macrophages. Here, we analyzed the pool of plasminogen in platelets and examined whether platelets express Plg-RKT. Plasminogen content of the supernatant of resting and collagen/thrombin-stimulated platelets was similar. Pretreatment with the lysine analog, ε-aminocaproic acid, significantly increased platelet-derived plasminogen (0.33 vs 0.08 nmol/108platelets) in the stimulated supernatant, indicating a lysine-dependent mechanism of membrane retention. Lysine-dependent, platelet-derived plasminogen retention on thrombin and convulxin activated human platelets was confirmed by flow cytometry. Platelets initiated fibrinolytic activity in fluorescently labeled plasminogen-deficient clots and in turbidimetric clot lysis assays. A 17-kDa band, consistent with Plg-RKT, was detected in the platelet membrane fraction by western blotting. Confocal microscopy of stimulated platelets revealed Plg-RKTcolocalized with plateletderived plasminogen on the activated platelet membrane. Plasminogen exposure was significantly attenuated in thrombin- and convulxin-stimulated platelets from Plg-RKT-/-mice compared with Plg-RKT+/+littermates. Membrane exposure of Plg-RKTwas not dependent on plasminogen, as similar levels of the receptor were detected in plasminogen-/-platelets. These data highlight Plg-RKTas a novel plasminogen receptor in human and murine platelets. We show for the first time that platelet-derived plasminogen is retained on the activated platelet membrane and drives local fibrinolysis by enhancing cell surface-mediated plasminogen activation.
Citation
WHYTE, C.S., MORROW, G.B., BAIK, N., BOOTH, N.A., JALAL, M.M., PARR, R.J. and MUTCH, N.J. 2021. Exposure of plasminogen and a novel plasminogen receptor, Plg-RKT, on activated human and murine platelets. Blood [online], 137(2), pages 248-257. Available from: https://doi.org/10.1182/blood.2020007263
| Journal Article Type | Article |
|---|---|
| Acceptance Date | Aug 15, 2020 |
| Online Publication Date | Aug 25, 2020 |
| Publication Date | Jan 14, 2021 |
| Deposit Date | Aug 7, 2023 |
| Publicly Available Date | Aug 14, 2023 |
| Journal | Blood |
| Print ISSN | 0006-4971 |
| Electronic ISSN | 1528-0020 |
| Publisher | American Society of Hematology |
| Peer Reviewed | Peer Reviewed |
| Volume | 137 |
| Issue | 2 |
| Pages | 248-257 |
| DOI | https://doi.org/10.1182/blood.2020007263 |
| Keywords | Platelets and thrombopoiesis; Thrombosis and hemostasis; Plasminogen; Plg-RKT; Platelets; Fibrinolysis |
| Public URL | https://rgu-repository.worktribe.com/output/2034912 |
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Publisher Licence URL
https://creativecommons.org/licenses/by-nc/4.0/
Copyright Statement
This research was originally published in Blood. WHYTE, C.S., MORROW, G.B., BAIK, N., BOOTH, N.A., JALAL, M.M., PARR, R.J. and MUTCH, N.J. 2021. Exposure of plasminogen and a novel plasminogen receptor, Plg-RKT, on activated human and murine platelets. Blood [online], 137(2), pages 248-257. © the American Society of Hematology.