title: SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages.
abstract: The lifespan of circulating red blood cells (RBCs) produced in bone marrow is determined by their elimination through phagocytosis by splenic macrophages. The mechanism by which RBC elimination is regulated has remained unclear, however. The surface glycoprotein SHPS-1, a member of the immunoglobulin superfamily, is abundant in macrophages. We have now examined the regulation of RBC turnover with the use of mice that express a mutant form of SHPS-1 lacking most of its cytoplasmic region. The mutant mice manifested mild anemia as well as splenomegaly characterized by expansion of the red pulp. The numbers of erythroid precursor cells in the spleen and of circulating reticulocytes were also increased in the mutant mice. In contrast, the half-life of circulating RBCs was reduced in these animals, and the rate of clearance of injected opsonized RBCs from the peripheral circulation was increased in association with their incorporation into splenic macrophages. Phagocytosis of opsonized RBCs by splenic macrophages from mutant mice in vitro was also increased compared with that observed with wild-type macrophages. These results suggest that SHPS-1 negatively regulates the phagocytosis of RBCs by splenic macrophages, thereby determining both the lifespan of individual RBCs and the number of circulating erythrocytes.
authors.affiliation: Department of Medicine and Clinical Scinece, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ishikawa-Sekigami
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Hideki
authors.initials: H
authors.lastname: Okazawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomizawa
authors.forename: Jun
authors.initials: J
authors.lastname: Okajo
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Chie
authors.initials: C
authors.lastname: Okuzawa
authors.forename: Minako
authors.initials: M
authors.lastname: Sugawara-Yokoo
authors.forename: Uichi
authors.initials: U
authors.lastname: Nishiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
mesh_terms: D000740:Anemia / Q000209:etiology; D000818:Animals; D004905:Erythrocyte Aging / Q000276:immunology; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000166:cytology; D004920:Erythropoiesis; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009895:Opsonin Proteins; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology* / Q000502:physiology; D013163:Splenomegaly / Q000209:etiology
chemical_list: D009895:Opsonin Proteins; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic