The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal
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Authors
Böse, JensGruber, Achim D
Helming, Laura
Schiebe, Stefanie
Wegener, Ivonne
Hafner, Martin
Beales, Marianne
Köntgen, Frank
Lengeling, Andreas
Issue Date
2004
Metadata
Show full item recordAbstract
Background Phagocytosis of apoptotic cells is fundamental to animal development, immune function and cellular homeostasis. The phosphatidylserine receptor (Ptdsr) on phagocytes has been implicated in the recognition and engulfment of apoptotic cells and in anti-inflammatory signaling. To determine the biological function of the phosphatidylserine receptor in vivo, we inactivated the Ptdsr gene in the mouse. Results Ablation of Ptdsr function in mice causes perinatal lethality, growth retardation and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. Ptdsr -/- mice with anophthalmia develop novel lesions, with induction of ectopic retinal-pigmented epithelium in nasal cavities. A comprehensive investigation of apoptotic cell clearance in vivo and in vitro demonstrated that engulfment of apoptotic cells was normal in Ptdsr knockout mice, but Ptdsr-deficient macrophages were impaired in pro- and anti-inflammatory cytokine signaling after stimulation with apoptotic cells or with lipopolysaccharide. Conclusion Ptdsr is essential for the development and differentiation of multiple organs during embryogenesis but not for apoptotic cell removal. Ptdsr may thus have a novel, unexpected developmental function as an important differentiation-promoting gene. Moreover, Ptdsr is not required for apoptotic cell clearance by macrophages but seems to be necessary for the regulation of macrophage cytokine responses. These results clearly contradict the current view that the phosphatidylserine receptor primarily functions in apoptotic cell clearance.Citation
Journal of Biology 2004 3(4):15Publisher
BioMed CentralDOI
10.1186/jbiol10PubMed ID
15345036PubMed Central ID
549712Language
en_USISSN
1478-58541475-4924
ae974a485f413a2113503eed53cd6c53
10.1186/jbiol10
Scopus Count
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