Publikationsdatenbank

The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal (2004)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Böse, Jens

Gruber, Achim D.

Helming, Laura

Schiebe, Stefanie

Wegener, Ivonne

Hafner, Martin

Beales, Marianne

Köntgen, Frank

Lengeling, Andreas

Quelle

Journal of biology

Bandzählung: 3

Heftzählung: 4

Seiten: 15

ISSN: 1475-4924

Sprache

Englisch

Verweise

URL (Volltext): https://jbiol.biomedcentral.com/articles/10.1186/jbiol10

DOI: 10.1186/jbiol10

Pubmed: 15345036

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.

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.

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.