Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Böse, Jens, Gruber, Achim D, Helming, Laura, Schiebe, Stefanie, Wegener, Ivonne, Hafner, Martin, Beales, Marianne, Köntgen, Frank, Lengeling, Andreas
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC549712/
https://www.ncbi.nlm.nih.gov/pubmed/15345036
http://dx.doi.org/10.1186/jbiol10
_version_ 1782122447090221056
author Böse, Jens
Gruber, Achim D
Helming, Laura
Schiebe, Stefanie
Wegener, Ivonne
Hafner, Martin
Beales, Marianne
Köntgen, Frank
Lengeling, Andreas
author_facet Böse, Jens
Gruber, Achim D
Helming, Laura
Schiebe, Stefanie
Wegener, Ivonne
Hafner, Martin
Beales, Marianne
Köntgen, Frank
Lengeling, Andreas
author_sort Böse, Jens
collection PubMed
description 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.
format Text
id pubmed-549712
institution National Center for Biotechnology Information
language English
publishDate 2004
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-5497122005-02-26 The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal Böse, Jens Gruber, Achim D Helming, Laura Schiebe, Stefanie Wegener, Ivonne Hafner, Martin Beales, Marianne Köntgen, Frank Lengeling, Andreas J Biol Research Article 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. BioMed Central 2004 2004-08-23 /pmc/articles/PMC549712/ /pubmed/15345036 http://dx.doi.org/10.1186/jbiol10 Text en Copyright © 2004 Böse et al., licensee BioMed Central Ltd.
spellingShingle Research Article
Böse, Jens
Gruber, Achim D
Helming, Laura
Schiebe, Stefanie
Wegener, Ivonne
Hafner, Martin
Beales, Marianne
Köntgen, Frank
Lengeling, Andreas
The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal
title The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal
title_full The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal
title_fullStr The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal
title_full_unstemmed The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal
title_short The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal
title_sort phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC549712/
https://www.ncbi.nlm.nih.gov/pubmed/15345036
http://dx.doi.org/10.1186/jbiol10
work_keys_str_mv AT bosejens thephosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT gruberachimd thephosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT helminglaura thephosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT schiebestefanie thephosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT wegenerivonne thephosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT hafnermartin thephosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT bealesmarianne thephosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT kontgenfrank thephosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT lengelingandreas thephosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT bosejens phosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT gruberachimd phosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT helminglaura phosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT schiebestefanie phosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT wegenerivonne phosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT hafnermartin phosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT bealesmarianne phosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT kontgenfrank phosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval
AT lengelingandreas phosphatidylserinereceptorhasessentialfunctionsduringembryogenesisbutnotinapoptoticcellremoval