Report
Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and beta2-integrin
| العنوان: | Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and beta2-integrin |
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| المؤلفون: | Konstantopoulos, K, Neelamegham, S, Burns, A. R, Hentzen, E, Kansas, G. S, Snapp, K. R, Berg, E. L, Hellums, J. D, Smith, C. W, McIntire, L. V, Simon, S. I |
| المصدر: | Circulation. 98(9) |
| بيانات النشر: | United States: NASA Center for Aerospace Information (CASI), 1998. |
| سنة النشر: | 1998 |
| مصطلحات موضوعية: | Life Sciences (General) |
| الوصف: | BACKGROUND: After activation, platelets adhere to neutrophils via P-selectin and beta2-integrin. The molecular mechanisms and adhesion events in whole blood exposed to venous levels of hydrodynamic shear in the absence of exogenous activation remain unknown. METHODS AND RESULTS: Whole blood was sheared at approximately 100 s(-1). The kinetics of neutrophil-platelet adhesion and neutrophil aggregation were measured in real time by flow cytometry. P-selectin was upregulated to the platelet surface in response to shear and was the primary factor mediating neutrophil-platelet adhesion. The extent of neutrophil aggregation increased linearly with platelet adhesion to neutrophils. Blocking either P-selectin, its glycoprotein ligand PSGL-1, or both simultaneously by preincubation with a monoclonal antibody resulted in equivalent inhibition of neutrophil-platelet adhesion (approximately 30%) and neutrophil aggregation (approximately 70%). The residual amount of neutrophil adhesion was blocked with anti-CD11b/CD18. Treatment of blood with prostacyclin analogue ZK36374, which raises cAMP levels in platelets, blocked P-selectin upregulation and neutrophil aggregation to baseline. Complete abrogation of platelet-neutrophil adhesion required both ZK36374 and anti-CD18. Electron microscopic observations of fixed blood specimens revealed that platelets augmented neutrophil aggregation both by forming bridges between neutrophils and through contact-mediated activation. CONCLUSIONS: The results are consistent with a model in which venous levels of shear support platelet adherence to neutrophils via P-selectin binding PSGL-1. This interaction alone is sufficient to mediate neutrophil aggregation. Abrogation of platelet adhesion and aggregation requires blocking Mac-1 in addition to PSGL-1 or P-selectin. The described mechanisms are likely of key importance in the pathogenesis and progression of thrombotic disorders that are exacerbated by leukocyte-platelet aggregation. |
| نوع الوثيقة: | Report |
| اللغة: | English |
| تدمد: | 0009-7322 |
| URL الوصول: | https://ntrs.nasa.gov/citations/20040172566 |
| ملاحظات: | HL-18672 NS-23327 AI31545-01 |
| رقم الانضمام: | edsnas.20040172566 |
| قاعدة البيانات: | NASA Technical Reports |
Full Text Finder | تدمد: | 00097322 |
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