| First Author | Kim K | Year | 2013 |
| Journal | Blood | Volume | 122 |
| Issue | 6 | Pages | 1052-61 |
| PubMed ID | 23788140 | Mgi Jnum | J:202279 |
| Mgi Id | MGI:5517769 | Doi | 10.1182/blood-2013-03-492504 |
| Citation | Kim K, et al. (2013) Platelet protein disulfide isomerase is required for thrombus formation but not for hemostasis in mice. Blood 122(6):1052-61 |
| abstractText | Protein disulfide isomerase (PDI) derived from intravascular cells is required for thrombus formation. However, it remains unclear whether platelet PDI contributes to the process. Using platelet-specific PDI-deficient mice, we demonstrate that PDI-null platelets have defects in aggregation and adenosine triphosphate secretion induced by thrombin, collagen, and adenosine diphosphate. Such defects were rescued by wild-type but not mutant PDI, indicating that the isomerase activity of platelet surface PDI is critical for the regulatory effect. PDI-deficient platelets expressed increased levels of intracellular ER protein 57 (ERp57) and ERp72. Platelet PDI regulated alphaIIbbeta3 integrin activation but not P-selectin exposure, Ca(2+) mobilization, beta3-talin1 interaction, or platelet spreading on immobilized fibrinogen. Inhibition of ERp57 further diminished alphaIIbbeta3 integrin activation and aggregation of activated PDI-deficient platelets, suggesting distinct roles of PDI and ERp57 in platelet functions. We found that platelet PDI is important for thrombus formation on collagen-coated surfaces under shear. Intravital microscopy demonstrates that platelet PDI is important for platelet accumulation but not initial adhesion and fibrin generation following laser-induced arteriolar injury. Tail bleeding time in platelet-specific PDI-deficient mice were not significantly increased. Our results provide important evidence that platelet PDI is essential for thrombus formation but not for hemostasis in mice. |
