title: Impaired splenic erythropoiesis in phlebotomized mice injected with CL2MDP-liposome: an experimental model for studying the role of stromal macrophages in erythropoiesis.
abstract: Erythropoiesis occurs in the presence of erythropoietin (EPO) without macrophages in vitro. In hematopoietic tissues, however, erythroid cells associate closely with stromal macrophages, forming erythroblastic islands via interactions with adhesion molecules. To elucidate the role of macrophages in erythropoiesis, we selectively abrogated stromal macrophages of splenic red pulp of phlebotomized mice by injection with dichloromethylene diphosphonate encapsulated in multilamellar liposomes (CL2MDP-liposome). In the spleen, no erythropoietic activity occurred until 5 days after the treatment. Colony assay revealed that the erythropoiesis was suppressed at the level of CFU-E. The splenic erythropoietic activity gradually developed from day 6 after the treatment, when F4/80+ macrophages began to appear in the red pulp. EPO mRNA was expressed in kidney but not in liver or spleen of phlebotomized mice injected with CL2MDP-liposome, and the serum EPO concentration in these mice was higher than that in phlebotomized mice. These findings suggest that abrogation of stromal macrophages by injection with CL2MDP-liposome impairs the splenic microenvironment for erythropoiesis induced by hypoxic stress, and this may be an excellent experimental model for further characterization of the in vivo role of splenic macrophages in erythropoiesis.
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Japan. sadapath@med.kawasaki-m.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Sadahira
authors.forename: T
authors.initials: T
authors.lastname: Yasuda
authors.forename: T
authors.initials: T
authors.lastname: Yoshino
authors.forename: T
authors.initials: T
authors.lastname: Manabe
authors.forename: T
authors.initials: T
authors.lastname: Takeishi
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Ebe
authors.forename: M
authors.initials: M
authors.lastname: Naito
mesh_terms: D000740:Anemia / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D003114:Colony-Forming Units Assay; D003864:Depression, Chemical; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D006470:Hemorrhage / Q000150:complications / Q000503:physiopathology; D006801:Humans; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018962:Phlebotomy; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins; D013154:Spleen / Q000187:drug effects* / Q000503:physiopathology; D017154:Stromal Cells / Q000502:physiology
chemical_list: D008081:Liposomes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004002:Clodronic Acid; D004921:Erythropoietin