Identification of a functional receptor for granulocyte colony-stimulating factor on platelets.

Abstract

Since granulocyte colony-stimulating factor (G-CSF) is thought to be a granulocyte lineage-specific cytokine, G-CSF receptors on blood cells other than those of granulocyte or monocyte lineage have not been well investigated. We now report that G-CSF receptors are present on platelets. The expression of G-CSF receptors on platelets was demonstrated by flow cytometry and radioreceptor assay. The mean number of G-CSF-binding sites per cell was 41 and the binding affinity was high (Kd 300 pM), similar to the affinity observed on granulocytes. Cross-linking assay revealed that G-CSF receptors were present on a single subunit protein of approximately 150 kD on the platelets. To clarify whether or not G-CSF might produce some direct functional influence on platelet response, the effects on platelet aggregation were studied. Although G-CSF itself did not affect platelet aggregation in vitro, preincubation with G-CSF augmented a secondary aggregation of platelets induced by low concentrations of adenosine diphosphate (ADP). There was a dose-response relationship for this G-CSF activity at concentrations of up to 10 ng/ml. Furthermore, the augmented ADP-induced secondary aggregation of platelets on G-CSF receptors was completely abrogated in the presence of anti-G-CSF polyclonal antibodies. These results indicate that platelets possess functional G-CSF receptors. (J.

Thrombopoietin, c‐Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and STAT3, and enhances agonists‐induced aggregation in platelets in vitro

“…IL-lfl and IFN-y enhance the adhesion of thrombin-treated platelets to monocytic leukemia cells, U937, and the release of serotonin by thrombin [25]. G-CSF augments the secondary aggregation of platelets induced by ADP [26]. PDGF inhibited collagen-or thrombin-induced aggregation [27] and secretion of ADP or fl-hexosaminidase in an autocrine manner [28].…”

Effects of mpl ligands on platelet production and function in nonhuman primates

“…However, similar proaggregatory effects are produced by other hematopoietic growth factors, including rHuG-CSF and stem cell factor [45,46]. Studies have been carried out assessing ex vivo aggregatory responsiveness of platelets obtained from animals receiving PEG-rHuMGDF and rHuTPO [30,32,471.…”

A prospective study of G-CSF effects on hemostasis in allogeneic blood stem cell donors

“…Shimoda and others have shown that G-CSF receptors are present on the surface of platelets. 2,3 These receptors appear to be functional in vitro 2 and in vivo 4,5 in healthy volunteers. However, the consequences on hemostasis of these findings are conflicting.…”

“…Other investigators have also observed an increase in platelet aggregation, in platelet activation, in von Willebrand factor and in thrombin-antithrombin complex after G-CSF, but these results could not be confirmed. 2,[4][5][6][7][8][9][10] To date, two cases of thrombosis occurring in normal donors have been reported. 11 The first one was a healthy 54-year-old woman who developed a cerebrovascular accident 2 days after completing an uneventful stem cell donation.…”