Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phosphatidylserine receptor.
Clearance of apoptotic cells by macrophages is considered important for prevention of inflammatory responses leading to tissue damage. The phosphatidylserine receptor (PSR), which specifically binds to phosphatidylserine (PS) exposed on the surface of apoptotic cells, mediates uptake of apoptotic cells in vitro, yet the physiologic relevance of PSR remains unknown. This issue was addressed by generating PSR-deficient (PSR(-/-)) mice. PSR(-/-) mice exhibited severe anemia and died during the perinatal period. In the PSR(-/-) fetal livers, erythroid differentiation was blocked at an early erythroblast stage. In addition, PSR(-/-) embryos exhibited thymus atrophy owing to a developmental defect of T-lymphoid cells. Clearance of apoptotic cells by macrophages was impaired in both liver and thymus of PSR(-/-) embryos. However, this did not induce up-regulation of inflammatory cytokines. These results indicate that during embryonic development, PSR-mediated apoptotic cell uptake is required for definitive erythropoiesis and T lymphopoiesis, independently of the prevention of inflammatory responses.
Kunisaki
Yuya
Y
Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Masuko
Sadahiko
S
Noda
Mayuko
M
Inayoshi
Ayumi
A
Sanui
Terukazu
T
Harada
Mine
M
Sasazuki
Takehiko
T
Fukui
Yoshinori
Y
D000740:Anemia / Q000209:etiology; D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D004622:Embryo, Mammalian; D004920:Erythropoiesis; D008099:Liver / Q000166:cytology* / Q000196:embryology; D038041:Lymphopoiesis; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000172:deficiency*; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000254:growth & development / Q000473:pathology
C498708:Ptdsr protein, mouse; D011956:Receptors, Cell Surface; C408123:phosphatidylserine receptor