Stimulation of thrombocytopoiesis decreases platelet beta2 but not beta1 or beta3 integrins.
The expression of CD29, CD61, CD18 and CD11a on platelets was examined by flow cytometry in mice treated with leukaemia inhibitory factor (LIF) or megakaryocyte growth and development factor (PEG-rHuMGDF or mpl-ligand). Treatment for 7-14 d with PEG-rHuMGDF or LIF increased the number of platelets in peripheral blood from 0.9 up to <2.0 x 10(6)/microl. These treatments decreased the expression of CD11a and CD18, whereas that of CD29 or CD61 was not markedly changed. Study after various doses or times of PEG-rHuMGDF administration indicated that a decrease of CD18 expression occurred when platelet counts started to rise. Platelet RNA content was increased in mice treated with PEG-rHuMGDF but double staining indicated that expression of CD18 was not correlated with RNA content. To evaluate integrin expression as a function of time in circulation, platelets were biotinylated in vivo. In normal or PEG-rHuMGDF-treated mice, the expression of CD29 or CD61 did not change, whereas that of CD18 decreased significantly as a function of time in circulation. These findings indicate, firstly, that stimulation of thrombocytopoiesis leads to the release of platelets with a low content of beta2 integrin and, secondly, that this integrin is also selectively lost while in the circulation.
Guo
J
J
Amgen Inc., Thousand Oaks, California, USA.
Piguet
P F
PF
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism*; D018845:CD11 Antigens; D018821:CD18 Antigens / Q000378:metabolism; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000494:pharmacology*; D039001:Integrin alpha Chains; D039222:Integrin alpha1beta1; D039661:Integrin beta3; D016023:Integrins / Q000378:metabolism*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism; D016024:Receptors, Cytoadhesin; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D006131:Growth Inhibitors; C406812:ITGAD protein, human; D039001:Integrin alpha Chains; D039222:Integrin alpha1beta1; D039661:Integrin beta3; D016023:Integrins; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D010980:Platelet Membrane Glycoproteins; D016024:Receptors, Cytoadhesin; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D012313:RNA; D013926:Thrombopoietin