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Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells.

Hoffmann PR, deCathelineau AM, Ogden CA, Leverrier Y, Bratton DL, Daleke DL, Ridley AJ, Fadok VA, Henson PM - J. Cell Biol. (2001)

Bottom Line: Further, recognition of PS was found to be dependent on the presence of the PS receptor (PSR).Both PS and anti-PSR antibodies stimulated membrane ruffling, vesicle formation, and "bystander" uptake of cells bound to the surface of the phagocyte.We propose that the phagocytosis of apoptotic cells requires two events: tethering followed by PS-stimulated, PSR-mediated macropinocytosis.

View Article: PubMed Central - PubMed

Affiliation: Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.

ABSTRACT
Efficient phagocytosis of apoptotic cells is important for normal tissue development, homeostasis, and the resolution of inflammation. Although many receptors have been implicated in the clearance of apoptotic cells, the roles of these receptors in the engulfment process have not been well defined. We developed a novel system to distinguish between receptors involved in tethering of apoptotic cells versus those inducing their uptake. Our results suggest that regardless of the receptors engaged on the phagocyte, ingestion does not occur in the absence of phosphatidylserine (PS). Further, recognition of PS was found to be dependent on the presence of the PS receptor (PSR). Both PS and anti-PSR antibodies stimulated membrane ruffling, vesicle formation, and "bystander" uptake of cells bound to the surface of the phagocyte. We propose that the phagocytosis of apoptotic cells requires two events: tethering followed by PS-stimulated, PSR-mediated macropinocytosis.

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Many proposed phagocytic receptors promote tethering, but not engulfment. Ebab targeting various receptors on the surface of HMDM were used to investigate the role of the receptors in binding versus uptake. All results represent mean ± SEM from three or more experiments. (A) Ebab coated with antibodies against several phagocytic receptors, either individually or in combination, tethered to HMDM, but were not efficiently engulfed. (B) Ebab coated with antibodies against the αvβ5 integrin also demonstrated tethering to HMDM with little uptake. (C) Ebab coated with vitronectin or thrombospondin, natural ligands for αvβ3 integrin or αvβ3/CD36, respectively, were not efficiently engulfed by HMDM. (D) Ebab coated with anti-SRA antibodies, tethered to murine macrophages, but were not efficiently engulfed compared with positive controls. ▪, Engulfed; □, tethered.
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fig2: Many proposed phagocytic receptors promote tethering, but not engulfment. Ebab targeting various receptors on the surface of HMDM were used to investigate the role of the receptors in binding versus uptake. All results represent mean ± SEM from three or more experiments. (A) Ebab coated with antibodies against several phagocytic receptors, either individually or in combination, tethered to HMDM, but were not efficiently engulfed. (B) Ebab coated with antibodies against the αvβ5 integrin also demonstrated tethering to HMDM with little uptake. (C) Ebab coated with vitronectin or thrombospondin, natural ligands for αvβ3 integrin or αvβ3/CD36, respectively, were not efficiently engulfed by HMDM. (D) Ebab coated with anti-SRA antibodies, tethered to murine macrophages, but were not efficiently engulfed compared with positive controls. ▪, Engulfed; □, tethered.

Mentions: Using this system, it was determined that engagement of putative apoptotic cell receptors including anti-CD36, anti-αvβ3 integrin (CD51/61), anti-CD14, and anti-CD68 resulted in binding of the erythrocytes to the macrophages without substantial uptake. Combining antibodies against CD36 with those against the VnR (CD51/61) did not significantly increase uptake (Fig. 2 A). Recently the αvβ5 integrin has been described as mediating uptake of apoptotic cells by dendritic cells (Albert et al., 1998, 2000). However, engagement of this receptor using our system also promoted tethering with no uptake by HMDM (Fig. 2 B).


Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells.

Hoffmann PR, deCathelineau AM, Ogden CA, Leverrier Y, Bratton DL, Daleke DL, Ridley AJ, Fadok VA, Henson PM - J. Cell Biol. (2001)

Many proposed phagocytic receptors promote tethering, but not engulfment. Ebab targeting various receptors on the surface of HMDM were used to investigate the role of the receptors in binding versus uptake. All results represent mean ± SEM from three or more experiments. (A) Ebab coated with antibodies against several phagocytic receptors, either individually or in combination, tethered to HMDM, but were not efficiently engulfed. (B) Ebab coated with antibodies against the αvβ5 integrin also demonstrated tethering to HMDM with little uptake. (C) Ebab coated with vitronectin or thrombospondin, natural ligands for αvβ3 integrin or αvβ3/CD36, respectively, were not efficiently engulfed by HMDM. (D) Ebab coated with anti-SRA antibodies, tethered to murine macrophages, but were not efficiently engulfed compared with positive controls. ▪, Engulfed; □, tethered.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2198875&req=5

fig2: Many proposed phagocytic receptors promote tethering, but not engulfment. Ebab targeting various receptors on the surface of HMDM were used to investigate the role of the receptors in binding versus uptake. All results represent mean ± SEM from three or more experiments. (A) Ebab coated with antibodies against several phagocytic receptors, either individually or in combination, tethered to HMDM, but were not efficiently engulfed. (B) Ebab coated with antibodies against the αvβ5 integrin also demonstrated tethering to HMDM with little uptake. (C) Ebab coated with vitronectin or thrombospondin, natural ligands for αvβ3 integrin or αvβ3/CD36, respectively, were not efficiently engulfed by HMDM. (D) Ebab coated with anti-SRA antibodies, tethered to murine macrophages, but were not efficiently engulfed compared with positive controls. ▪, Engulfed; □, tethered.
Mentions: Using this system, it was determined that engagement of putative apoptotic cell receptors including anti-CD36, anti-αvβ3 integrin (CD51/61), anti-CD14, and anti-CD68 resulted in binding of the erythrocytes to the macrophages without substantial uptake. Combining antibodies against CD36 with those against the VnR (CD51/61) did not significantly increase uptake (Fig. 2 A). Recently the αvβ5 integrin has been described as mediating uptake of apoptotic cells by dendritic cells (Albert et al., 1998, 2000). However, engagement of this receptor using our system also promoted tethering with no uptake by HMDM (Fig. 2 B).

Bottom Line: Further, recognition of PS was found to be dependent on the presence of the PS receptor (PSR).Both PS and anti-PSR antibodies stimulated membrane ruffling, vesicle formation, and "bystander" uptake of cells bound to the surface of the phagocyte.We propose that the phagocytosis of apoptotic cells requires two events: tethering followed by PS-stimulated, PSR-mediated macropinocytosis.

View Article: PubMed Central - PubMed

Affiliation: Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.

ABSTRACT
Efficient phagocytosis of apoptotic cells is important for normal tissue development, homeostasis, and the resolution of inflammation. Although many receptors have been implicated in the clearance of apoptotic cells, the roles of these receptors in the engulfment process have not been well defined. We developed a novel system to distinguish between receptors involved in tethering of apoptotic cells versus those inducing their uptake. Our results suggest that regardless of the receptors engaged on the phagocyte, ingestion does not occur in the absence of phosphatidylserine (PS). Further, recognition of PS was found to be dependent on the presence of the PS receptor (PSR). Both PS and anti-PSR antibodies stimulated membrane ruffling, vesicle formation, and "bystander" uptake of cells bound to the surface of the phagocyte. We propose that the phagocytosis of apoptotic cells requires two events: tethering followed by PS-stimulated, PSR-mediated macropinocytosis.

Show MeSH
Related in: MedlinePlus