Home LiteratureArticle Details
PMID: 16908670 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages.

The Journal of cell biology ·Vol. 174 ·No. 4 ·2006-08-14 ·Pages 547-56

Jehle AW, Gardai SJ, Li S, Linsel-Nitschke P, Morimoto K, Janssen WJ, Vandivier RW, Wang N, Greenberg S, Dale BM, Qin C, Henson PM, Tall AR

Abstract

The mammalian ATP-binding cassette transporters A1 and A7 (ABCA1 and -A7) show sequence similarity to CED-7, a Caenorhabditis elegans gene that mediates the clearance of apoptotic cells. Using RNA interference or gene targeting, we show that knock down of macrophage ABCA7 but not -A1 results in defective engulfment of apoptotic cells. In response to apoptotic cells, ABCA7 moves to the macrophage cell surface and colocalizes with the low-density lipoprotein receptor-related protein 1 (LRP1) in phagocytic cups. The cell surface localization of ABCA7 and LRP1 is defective in ABCA7-deficient cells. C1q is an opsonin of apoptotic cells that acts via phagocyte LRP1 to induce extracellular signal-regulated kinase (ERK) signaling. We show that ERK signaling is required for phagocytosis of apoptotic cells and that ERK phosphorylation in response to apoptotic cells or C1q is defective in ABCA7-deficient cells. These studies reveal a major role of ABCA7 and not -A1 in the clearance of apoptotic cells and therefore suggest that ABCA7 is an authentic orthologue of CED-7.

MeSH Terms
ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters/genetics,metabolism Animals Apoptosis/physiology Caenorhabditis elegans Proteins/metabolism Cell Membrane/metabolism Cells, Cultured Complement C1q/metabolism Down-Regulation/physiology Extracellular Signal-Regulated MAP Kinases/metabolism Female Gene Targeting Humans Low Density Lipoprotein Receptor-Related Protein-1 MAP Kinase Signaling System/physiology Macrophages/metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Phagocytosis/physiology RNA Interference Receptors, LDL/metabolism Tumor Suppressor Proteins/metabolism Up-Regulation/physiology
Chemicals
ABCA1 protein, human ABCA7 protein, human ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters CED-7 protein, C elegans Caenorhabditis elegans Proteins Low Density Lipoprotein Receptor-Related Protein-1 Lrp1 protein, mouse Receptors, LDL Tumor Suppressor Proteins Complement C1q Extracellular Signal-Regulated MAP Kinases
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Jehle Andreas W
Department of Medicine, Columbia University, New York, NY 10032, USA. [email protected]
Gardai Shyra J
Li Suzhao
Linsel-Nitschke Patrick
Morimoto Konosuke
Janssen William J
Vandivier R William
Wang Nan
Greenberg Steven
Dale Benjamin M
Qin Chunbo
Henson Peter M
Tall Alan R
References (40)
40 references, click to expand
  1. Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex.
    J Immunol. 2002 Oct 1;169(7):3978-86 PMID: 12244199
  2. Thrombospondin stimulates focal adhesion disassembly through Gi- and phosphoinositide 3-kinase-dependent ERK activation.
    J Biol Chem. 2002 Jun 7;277(23):20453-60 PMID: 11923291
  3. Mechanisms in LPA-induced tumor cell migration: critical role of phosphorylated ERK.
    J Cell Sci. 2003 Sep 15;116(Pt 18):3835-46 PMID: 12902401
  4. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation.
    Cell. 2003 Oct 3;115(1):13-23 PMID: 14531999
  5. ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux.
    J Biol Chem. 2003 Oct 31;278(44):42906-12 PMID: 12917409
  6. The final step in programmed cell death: phagocytes carry apoptotic cells to the grave.
    Essays Biochem. 2003;39:105-17 PMID: 14585077
  7. Actin reorganization and morphological changes in human neutrophils stimulated by TNF, GM-CSF, and G-CSF: the role of MAP kinases.
    Am J Physiol Cell Physiol. 2004 Jan;286(1):C55-64 PMID: 12954601
  8. The engulfment process of programmed cell death in caenorhabditis elegans.
    Annu Rev Cell Dev Biol. 2004;20:193-221 PMID: 15473839
  9. Modulation of multiple neutrophil functions by preparative methods or trace concentrations of bacterial lipopolysaccharide.
    Am J Pathol. 1985 Apr;119(1):101-10 PMID: 2984939
  10. LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation.
    Cell. 1992 Oct 30;71(3):411-21 PMID: 1423604
  11. Phosphatidylcholine translocase: a physiological role for the mdr2 gene.
    Cell. 1994 Jul 1;77(7):1071-81 PMID: 7912658
  12. The ATP binding cassette transporter ABC1, is required for the engulfment of corpses generated by apoptotic cell death.
    EMBO J. 1996 Jan 15;15(2):226-35 PMID: 8617198
  13. Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes.
    J Exp Med. 1997 Nov 3;186(9):1487-94 PMID: 9348306
  14. Mitogen-activated protein kinase is activated during IgG-mediated phagocytosis, but is not required for target ingestion.
    Inflammation. 1998 Feb;22(1):67-82 PMID: 9484651
  15. The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC transporters.
    Cell. 1998 Jun 12;93(6):951-60 PMID: 9635425
  16. Oxidant stress incites spreading of macrophages via extracellular signal-regulated kinases and p38 mitogen-activated protein kinase.
    J Immunol. 1998 Oct 1;161(7):3569-74 PMID: 9759878
  17. CD36 is required for phagocytosis of apoptotic cells by human macrophages that use either a phosphatidylserine receptor or the vitronectin receptor (alpha v beta 3).
    J Immunol. 1998 Dec 1;161(11):6250-7 PMID: 9834113
  18. Mechanisms of phagocytosis in macrophages.
    Annu Rev Immunol. 1999;17:593-623 PMID: 10358769
  19. Thrombospondin induces RhoA inactivation through FAK-dependent signaling to stimulate focal adhesion disassembly.
    J Biol Chem. 2004 Nov 19;279(47):48983-92 PMID: 15371459
  20. Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells.
    Mol Biol Cell. 2004 Dec;15(12):5399-407 PMID: 15469992
  21. Tyrosine phosphorylation of the LDL receptor-related protein (LRP) and activation of the ERK pathway are required for connective tissue growth factor to potentiate myofibroblast differentiation.
    FASEB J. 2004 Dec;18(15):1920-1 PMID: 15469966
  22. Potential role of ABCA7 in cellular lipid efflux to apoA-I.
    J Lipid Res. 2005 Jan;46(1):86-92 PMID: 15520449
  23. Abca7 null mice retain normal macrophage phosphatidylcholine and cholesterol efflux activity despite alterations in adipose mass and serum cholesterol levels.
    J Biol Chem. 2005 Feb 4;280(5):3989-95 PMID: 15550377
  24. Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans.
    Nature. 2005 Mar 3;434(7029):93-9 PMID: 15744306
  25. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte.
    Cell. 2005 Oct 21;123(2):321-34 PMID: 16239148
  26. TNFalpha induces ABCA1 through NF-kappaB in macrophages and in phagocytes ingesting apoptotic cells.
    Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3112-7 PMID: 16492740
  27. Involvement of mitogen-activated protein kinases in class B scavenger receptor type I-induced phagocytosis of apoptotic cells.
    Exp Cell Res. 2006 Jun 10;312(10):1820-30 PMID: 16530182
  28. Lovastatin enhances clearance of apoptotic cells (efferocytosis) with implications for chronic obstructive pulmonary disease.
    J Immunol. 2006 Jun 15;176(12):7657-65 PMID: 16751413
  29. Regulation of polymorphonuclear leukocyte phagocytosis by myosin light chain kinase after activation of mitogen-activated protein kinase.
    Blood. 2000 Apr 1;95(7):2407-12 PMID: 10733514
  30. Heart, brain, and body wall defects in mice lacking calreticulin.
    Exp Cell Res. 2000 Apr 10;256(1):105-11 PMID: 10739657
  31. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine.
    Nat Cell Biol. 2000 Jul;2(7):399-406 PMID: 10878804
  32. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo.
    J Exp Med. 2000 Aug 7;192(3):359-66 PMID: 10934224
  33. Engulfment of apoptotic cells involves the redistribution of membrane phosphatidylserine on phagocyte and prey.
    Nat Cell Biol. 1999 Nov;1(7):454-6 PMID: 10559991
  34. LRP: a multifunctional scavenger and signaling receptor.
    J Clin Invest. 2001 Sep;108(6):779-84 PMID: 11560943
  35. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells.
    J Exp Med. 2001 Sep 17;194(6):781-95 PMID: 11560994
  36. Apoptotic cell removal.
    Curr Biol. 2001 Oct 2;11(19):R795-805 PMID: 11591341
  37. Contrasting requirements for ubiquitylation during Fc receptor-mediated endocytosis and phagocytosis.
    EMBO J. 2002 Feb 1;21(3):251-8 PMID: 11823418
  38. Interaction of CED-6/GULP, an adapter protein involved in engulfment of apoptotic cells with CED-1 and CD91/low density lipoprotein receptor-related protein (LRP).
    J Biol Chem. 2002 Apr 5;277(14):11772-9 PMID: 11729193
  39. Resolution of lung inflammation by CD44.
    Science. 2002 Apr 5;296(5565):155-8 PMID: 11935029
  40. Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly.
    J Cell Biol. 2003 Jun 23;161(6):1179-89 PMID: 12821648
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200601030
Email
[email protected]
Published
2006-08-14
Pages
547-56
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2064260
Subset
IM
Grants
NHLBI NIH HHS · HL22682 · United States
NHLBI NIH HHS · R01 HL022682 · United States
NHLBI NIH HHS · HL84555 · United States
PHS HHS · PN0503-104 · United States
NHLBI NIH HHS · R37 HL022682 · United States
NHLBI NIH HHS · HL54164 · United States
NIGMS NIH HHS · R01 GM061031 · United States
NHLBI NIH HHS · R01 HL054164 · United States
NIGMS NIH HHS · GM61031 · United States
External Links
PubMed source DOI: 10.1083/jcb.200601030 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2