Platelets Release Thrombopoietin (Tpo) upon Activation: another Regulatory Loop in Thrombocytopoiesis?

Abstract

SummaryThrombopoietin is produced at a constant rate by the liver and kidney and is removed from the circulation upon binding and subsequent uptake via the Tpo receptor, c-Mpl, expressed by platelets and megakaryocytes. Apart from uptake, this study shows that platelets can also function as a storage pool for Tpo.Upon stimulation with various platelet agonists, full-length biologically active Tpo was released by platelets. Platelet fractionation experiments indicated that this Tpo most likely is contained in the granules. When platelets were preincubated with Tpo-peptide mimetic or truncated Tpo prior to maximal activation, a three- to fivefold increment in Tpo release was seen, whereas, the release of other granule proteins such as vWF-propeptide or serotonin remained unchanged. Therefore, the Mpl agonists might compete with Mpl-bound Tpo, thereby releasing Tpo into the platelet supernatant.Intravascular release of Tpo by platelets might occur in patients with massive platelet activation, as occurs in patients with disseminated intravascular coagulation. The Tpo concentration in these patients is elevated (p <0.01) and correlates with markers for thrombin generation, TAT complexes and Fl+2 (rp =0.8 and 0.9; p <0.01). This suggests that the increment in Tpo concentration was attributed to Tpo release by activated platelets in vivo, which might be instrumental in subsequent stimulation of thrombocytopoiesis.

Prognostic Significance of Thrombocytosis in Node-negative Colon Cancer

“…19 Platelets contain thrombopoietin and release it on activation. 20 This plateletreleased thrombopoietin stimulates the bone marrow to generate new platelets and release them into the circulation. Thrombocytosis may adversely affect patient survival because of interactions between platelets and tumour cells.…”

Significance of Thrombocytosis in Clinicopathologic Characteristics and Prognosis of Gastric Cancer

“…Activated platelets also secrete TPO further, which stimulates bone marrow to generate new platelets. Thus, platelets and cancer cells make up a positive feedback cascade in which each stimulates the other, potentiating the effect (Folman et al, 2000).…”

Thrombopoietin increases platelet adhesion under flow and decreases rolling

“…It is uncertain whether this is really the case. During prolonged incubation, the effect of TPO disappears, possibly as a result of receptor desensitization and uptake/degradation of receptor-bound TPO (Folman et al, 2000). Furthermore, inhibiting factors such as prostacyclin and nitric oxide are likely to override the activating properties of TPO.…”

“…There are about 60 cMpl receptors/platelet (Debili et al, 1995). Following ligand occupancy, the TPO-receptor complex is internalized and TPO is either degraded or stored in secretion granules (Folman et al, 2000). This uptake is thought to be crucial for the regulation of the TPO concentration in plasma (Kuter & Rosenberg, 1995).…”