title: Stimulation of thrombocytopoiesis decreases platelet beta2 but not beta1 or beta3 integrins.
abstract: 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.
authors.affiliation: Amgen Inc., Thousand Oaks, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: P F
authors.initials: PF
authors.lastname: Piguet
mesh_terms: 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*
chemical_list: 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