| Abstract | Glu-plasminogen, the native form of plasminogen, interacts in a specific and saturable manner with unstimulated human platelets, and the binding is enhanced fivefold by thrombin stimulation (Miles and Plow, 1985. J. Biol. Chem. 260:4303). This study characterizes the nature of the Glu-plasminogen binding sites by analyzing platelets deficient in selected proteins and functions. Platelets from patients with afibrinogenemia, Gray platelet syndrome, and the Cam Variant of thrombasthenia, a form of thrombasthenia with near normal levels of glycoprotein IIb/IIIa (GPIIb/IIIa), showed minimal augmentation of plasminogen binding to thrombin-stimulated platelets but normal binding to unstimulated platelets. This selective deficiency indicates that two distinct mechanisms are involved in the interaction of plasminogen with platelets. These abnormal platelets share a deficiency in fibrinogen. Surface expression of platelet fibrinogen, however, was not sufficient for enhanced plasminogen binding to stimulated platelets, and experiments with alpha-thrombin and gamma-thrombin indicated that fibrin formation on the platelet surface is necessary for the augmented plasminogen binding. Unstimulated and stimulated thrombasthenic platelets deficient in GPIIb/IIIa bound markedly reduced levels of plasminogen, which suggests a role for GPIIb/IIIa in plasminogen binding to unstimulated platelets. Treatment of platelets to dissociate the heterodimeric complex of GPIIb/IIIa did not significantly perturb plasminogen binding to unstimulated platelets, but the complex may be necessary for thrombin-stimulated plasminogen binding via its interaction with platelet fibrin. |
| Authors | L A Miles, M H Ginsberg, J G White, E F Plow |
| Journal | The Journal of clinical investigation
(J Clin Invest)
Vol. 77
Issue 6
Pg. 2001-9
(Jun 1986)
ISSN: 0021-9738 UNITED STATES |
| PMID | 3086385
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Immunoglobulin Fab Fragments
- Fibrinopeptide A
- Epinephrine
- Calcimycin
- Fibrinogen
- Plasminogen
- Thrombin
|
| Topics |
- Blood Platelets
(metabolism)
- Calcimycin
(pharmacology)
- Epinephrine
(pharmacology)
- Fibrinogen
(metabolism)
- Fibrinopeptide A
(metabolism)
- Humans
- Immunoglobulin Fab Fragments
- Molecular Weight
- Plasminogen
(metabolism)
- Thrombin
(pharmacology)
|
