Effect of thrombopoietin and granulocyte colony-stimulating factor on platelets and polymorphonuclear leukocytes

Thrombopoietin (TPO) and granulocyte colony-stimulating factor (G-CSF) may be administered together in aplastic patients. We evaluated the effect of b oth cytokines alone or combined on platelets and polymorphonuclear leukocyt es (PMN) functional responses. TPO, G-CSF, or the combination of both cytok ines, induced neither platelet nor PMN activation. TPO but not G-CSF synerg ized with threshold ADP concentrations to induce maximal aggregation and AT P release. The synergistic effect of TPO with ADP was not modified by the p resence of G-CSF, Flow cytometry studies have shown that thrombin-induced l oss of GPIb from platelet surface was significantly increased by pretreatme nt of platelets with TPO, G-CSF, or both cytokines. P-selectin expression i nduced by thrombin was augmented by TPO, but not by G-CSF, Coincubation of the cells with TPO and G-CSF did not modify the values obtained with TPO al one. Expression of CD116 on PMN surface was augmented by G-CSF or fMLP. G-C SF treated PMN increased the effect of fMLP on CD116 expression, TPO did no t modify either basal levels of CD116 or the increased expression induced b y G-CSF or fMLP, Incubation of PMN with both cytokines showed no difference s compared to G-CSF alone. Platelet-PMN aggregates induced by thrombin in w hole blood were augmented by TPO, G-CSF alone neither synergized with throm bin nor changed the results observed with TPO, These data show that in vitr o functional responses of platelets, or PMN induced by TPO or G-CSF alone, were neither further increased nor inhibited by treatment of the cells with both cytokines, (C) 2000 Elsevier Science Ltd, All rights reserved.