title: Hematologic effects of stem cell factor (SCF) and leukemia inhibitory factor (LIF) in vivo: LIF-induced thrombocytosis in SCF-primed mice.
abstract: Stem cell factor (SCF) administered as daily bolus injections in dose-response experiments in mice causes a progressive and dramatic dose-dependent panleukocytosis characterized by neutrophilia, eosinophilia, monocytosis, and lymphocytosis. SCF causes circulating platelet numbers to be dose-dependently increased after 2 weeks of daily injections. Leukemia inhibitory factor (LIF) administered as daily bolus injections in mice causes a peripheral leukopenia that is largely due to peripheral lymphopenia. LIF causes thrombocytosis peaking after approximately 1 w. Coinjection of SCF and LIF for 1 to 2 wk in mice does not cause a much greater thrombocytosis than the maximum thrombocytosis achievable with SCF or LIF alone. On the other hand, daily injection of SCF for 5 days followed by daily injection of LIF for 5 to 6 d in mice causes a very substantial increase in platelets that was lineage-specific in terms of not being accompanied by a generalized leukocytosis. In contrast, only a very modest thrombocytosis was noted in SCF-primed LIF-treated rats. LIF causes a large increase in the cytoplasmic volume of splenic megakaryocytes in mice, but not in rats. In conclusion, SCF-induced priming followed by LIF-induced maturation of megakaryocytes causes a substantial selective increase in the numbers of circulating platelets in mice.
authors.affiliation: Department of Pathology, UC San Diego School of Medicine, CA, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Ulich
authors.forename: J
authors.initials: J
authors.lastname: del Castillo
authors.forename: S S
authors.initials: SS
authors.lastname: Shin
authors.forename: S
authors.initials: S
authors.lastname: Yin
authors.forename: D
authors.initials: D
authors.lastname: Duryea
authors.forename: J
authors.initials: J
authors.lastname: Tarpley
authors.forename: B
authors.initials: B
authors.lastname: Samal
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000187:drug effects / Q000473:pathology*; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004802:Eosinophilia / Q000139:chemically induced*; D006131:Growth Inhibitors / Q000008:administration & dosage*; D016298:Hematopoietic Cell Growth Factors / Q000008:administration & dosage*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D019089:Stem Cell Factor
chemical_list: D006131:Growth Inhibitors; D016298:Hematopoietic Cell Growth Factors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D019089:Stem Cell Factor