title: Involvement of cross-linked ribosomal protein S19 oligomers and C5a receptor in definitive erythropoiesis.
abstract: We performed a series of experiments under a working hypothesis that cross-linked oligomers of ribosomal protein S19 (RP S19) play an essential role in definitive erythropoiesis as a ligand of the C5a receptor of erythroblasts and macrophages. We found molecules functionally and immunologically indistinguishable from RP S19 oligomers in the extracellular fluid of porcine and guinea pig bone marrow. When an increased hematopoietic state was induced in guinea pigs by bloodletting, the bone marrow RP S19 oligomer concentration was concomitantly increased. However, when the RP S19 oligomers were immunologically neutralized or the C5a receptor was pharmacologically antagonized, hyper-erythropoiesis induced by bloodletting was prevented and the anemic state was retarded in guinea pigs. When the RP S19 oligomers were neutralized in mice after bloodletting, the reactive hyper proliferation of erythroblasts in the spleen was prevented. Proerythroblasts and erythroblasts prepared by bone marrow aspiration from healthy individuals were found to express significant levels of the C5a receptor and type 2 transglutaminase genes. Majority of erythroblasts in cord blood of healthy newborns bore the C5a receptor. Taken together, these results support our hypothesis.
authors.affiliation: Department of Molecular Pathology, Faculty of Life Science and Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Umeko
authors.initials: U
authors.lastname: Semba
authors.forename: Masato
authors.initials: M
authors.lastname: Oda
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Ken
authors.initials: K
authors.lastname: Toba
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hattori
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing; D001815:Bloodletting; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003432:Cross-Linking Reagents; D015672:Erythroid Precursor Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004920:Erythropoiesis / Q000502:physiology*; D045604:Extracellular Fluid / Q000276:immunology / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000378:metabolism; D006168:Guinea Pigs; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D055503:Protein Multimerization; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D013552:Swine; D011503:Transglutaminases / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D003432:Cross-Linking Reagents; D006454:Hemoglobins; D044087:Receptor, Anaphylatoxin C5a; D012269:Ribosomal Proteins; C040343:ribosomal protein S19; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: APC; Bone marrow; C5a receptor; Erythroblast; Erythropoiesis; Extraribosomal function; FACS; FITC; HBSS; Hanks' balanced salt solution; PBGD; PBS; PE; RP S19; RT-PCR; Ribosomal protein S19; allophycocyanin; fluorescein isothiocyanate; fluorescence-activated cell sorting; phosphate-buffered saline; phycoerythrin; porphobilinogen deaminase; reverse transcriptase-polymerase chain reaction; ribosomal protein S19