Enhanced phagocytosis of CD47-deficient red blood cells by splenic macrophages requires SHPS-1.
The interaction of CD47 on red blood cells (RBCs) with SHPS-1 on macrophages is implicated to prevent the phagocytosis of the former cells by the latter cells. Indeed, the rate of clearance of transfused CD47-deficient (CD47(-/-)) RBCs from the bloodstream of wild-type mice was markedly increased compared with wild-type RBCs. Conversely, the rate of clearance of transfused wild-type RBCs was markedly increased in mice that expressed a mutant form of SHPS-1 lacking most of the cytoplasmic region of the protein. However, we here found that the clearance of CD47(-/-) RBCs in SHPS-1 mutant mice was minimal. In addition, the phagocytosis of CD47(-/-) RBCs by splenic macrophages from SHPS-1 mutant mice was markedly reduced compared with wild-type macrophages. These results thus suggest an additional role for CD47 on RBCs in the negative regulation of phagocytosis by macrophages and in determination of the life span of circulating RBCs.
Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan.
Tomomi
T
Ishikawa-Sekigami
Yoriaki
Y
Kaneko
Yasuyuki
Y
Saito
Yoji
Y
Murata
Hideki
H
Okazawa
Hiroshi
H
Ohnishi
Per-Arne
PA
Oldenborg
Yoshihisa
Y
Nojima
Takashi
T
Matozaki
D000818:Animals; D051928:CD47 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D010587:Phagocytosis / Q000502:physiology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology*
D051928:CD47 Antigen; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic