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

2.50
Hdl Handle:
http://hdl.handle.net/10033/8683
Title:
The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal
Authors:
Böse, Jens; Gruber, Achim D; Helming, Laura; Schiebe, Stefanie; Wegener, Ivonne; Hafner, Martin; Beales, Marianne; Köntgen, Frank; Lengeling, Andreas
Abstract:
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):15
Publisher:
BioMed Central
Issue Date:
2004
URI:
http://hdl.handle.net/10033/8683
DOI:
10.1186/jbiol10
PubMed ID:
15345036
PubMed Central ID:
549712
Additional Links:
http://jbiol.com/content/3/4/15; http://creativecommons.org/licenses/by/2.0
Language:
en_US
ISSN:
1478-5854; 1475-4924
Appears in Collections:
publications of the department infection genetics (INFG)

Full metadata record

DC FieldValue Language
dc.contributor.authorBöse, Jensen_US
dc.contributor.authorGruber, Achim Den_US
dc.contributor.authorHelming, Lauraen_US
dc.contributor.authorSchiebe, Stefanieen_US
dc.contributor.authorWegener, Ivonneen_US
dc.contributor.authorHafner, Martinen_US
dc.contributor.authorBeales, Marianneen_US
dc.contributor.authorKöntgen, Franken_US
dc.contributor.authorLengeling, Andreasen_US
dc.date.accessioned2007-02-21T08:21:20Z-
dc.date.available2004en_US
dc.date.available2007-02-21T08:21:20Z-
dc.date.issued2004en_US
dc.identifier.citationJournal of Biology 2004 3(4):15en_US
dc.identifier.issn1478-5854en_US
dc.identifier.issn1475-4924en_US
dc.identifier.pmid15345036en_US
dc.identifier.doi10.1186/jbiol10en_US
dc.identifier.urihttp://hdl.handle.net/10033/8683-
dc.description.abstractBackground 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.en_US
dc.language.isoen_US-
dc.publisherBioMed Centralen_US
dc.relation.urlhttp://jbiol.com/content/3/4/15en_US
dc.relation.urlhttp://creativecommons.org/licenses/by/2.0en_US
dc.rightsCopyright © 2004 Böse et al., licensee BioMed Central Ltd.en_US
dc.titleThe phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removalen_US
dc.identifier.pmcid549712en_US
dc.format.digYES-

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