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 both cytokines alone or combined on platelets and polymorphonuclear leukocytes (PMN) functional responses. TPO, G-CSF, or the combination of both cytokines, induced neither platelet nor PMN activation. TPO but not G-CSF synergized with threshold ADP concentrations to induce maximal aggregation and ATP release. The synergistic effect of TPO with ADP was not modified by the presence of G-CSF. Flow cytometry studies have shown that thrombin-induced loss of GPIb from platelet surface was significantly increased by pretreatment of platelets with TPO, G-CSF, or both cytokines. P-selectin expression induced 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 alone. Expression of CD11b on PMN surface was augmented by G-CSF or fMLP. G-CSF-treated PMN increased the effect of fMLP on CD11b expression. TPO did not modify either basal levels of CD11b or the increased expression induced by G-CSF or fMLP. Incubation of PMN with both cytokines showed no differences compared to G-CSF alone. Platelet-PMN aggregates induced by thrombin in whole blood were augmented by TPO. G-CSF alone neither synergized with thrombin nor changed the results observed with TPO. These data show that in vitro 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.
Schattner
M
M
Research Career, CONICET, Buenos Aires, Argentina. schattne@mail.retina.ar
Pozner
R G
RG
Gorostizaga
A B
AB
Lazzari
M A
MA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000187:drug effects; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D019007:P-Selectin / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*
D016177:Macrophage-1 Antigen; D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex; D016179:Granulocyte Colony-Stimulating Factor; D000244:Adenosine Diphosphate; D013926:Thrombopoietin; D013917:Thrombin