Skip to main content
SpringerLink
Log in

Upregulation of phagocytic clearance of apoptotic cells by autoimmune regulator

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

To investigate the effect of autoimmune regulator (AIRE) on phagocytic clearance of apoptotic cells, a recombinant expression vector containing full-length human AIRE cDNA was transfected into 16HBE cells. After incubation with transfected 16HBE cells, engulfment of apoptotic HL-60 cells induced by camptothecin was detected by myeloperoxidase (MPO) staining. The change in the expression of Rac 1 in transfected 16HBE cells was determined by RT-PCR and Western blotting. The results showed that the phagocytosis percentage of the experimental group, the mock transfection group and the negative control group (non-apoptotic cells) was (25.50±3.67)%, (6.25±1.58)% and (1.0±0.67)%, respectively. Moreover, the expressions of Rac 1 mRNA and protein were up-regulated in AIRE-transfected 16HBE cells, suggesting that AIRE may function as a regulator in the phagocytic clearance of apoptotic cells by promoting the expression of Rac 1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Betterle C, Greggio NA, Volpato M. Clinical review 93: Autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab, 1998, 83(4):1049–1055

    Article  CAS  PubMed  Google Scholar 

  2. International Union of Immunological Societies Expert Committee on Primary Immunodeficiencies, Notarangelo LD, Fischer A, et al. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol, 2009, 124(6):1161–1178

    Article  CAS  PubMed  Google Scholar 

  3. Finnish-German APECED Consortium. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet, 1997, 17(4):399–403

    Article  Google Scholar 

  4. Nagamine K, Peterson P, Scott HS, et al. Positional cloning of the APECED gene. Nat Genet, 1997, 17(4): 393–398

    Article  CAS  PubMed  Google Scholar 

  5. Heino M, Peterson P, Kudoh J, et al. Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla. Biochem Biophys Res Commun, 1999, 257(3): 821–825

    Article  CAS  PubMed  Google Scholar 

  6. Anderson MS, Venanzi ES, Chen Z, et al. The cellular mechanism of Aire control of T cell tolerance. Immunity, 2005, 23(2):227–239

    Article  CAS  PubMed  Google Scholar 

  7. Anderson MS, Venanzi ES, Klein L, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science, 2002, 298(5597):1395–1401

    Article  CAS  PubMed  Google Scholar 

  8. Kogawa K, Nagafuchi S, Katsuta H, et al. Expression of AIRE gene in peripheral monocyte/dendritic cell lineage. Immunol Lett, 2002, 80(3):195–198

    Article  CAS  PubMed  Google Scholar 

  9. Lauber K, Blumenthal SG, Waibel M, et al. Clearance of apoptotic cells: getting rid of the corpses. Mol Cell, 2004, 4(3):277–287

    Article  Google Scholar 

  10. Rosen A, Casciola-Rosen L. Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease. Cell Death Differ, 1999, 6(1):6–12

    Article  CAS  PubMed  Google Scholar 

  11. Albert ML, Jegathesan M, Darnell RB. Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells. Nat Immunol, 2001, 2(11):1010–1017

    Article  CAS  PubMed  Google Scholar 

  12. Huang FP, Platt N, Wykes M, et al. A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. J Exp Med, 2000, 191(3):435–444

    Article  CAS  PubMed  Google Scholar 

  13. Herrmann M, Voll RE, Zoller OM, et al. Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum, 1998, 41(7):1241–1250

    Article  CAS  PubMed  Google Scholar 

  14. Akiyoshi H, Hatakeyama S, Pitkänen J, et al. Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner. J Biol Chem, 2004, 279(32): 33984–33991

    Article  CAS  PubMed  Google Scholar 

  15. Hachiya M, Osawa Y, Akashi M. Role of TNFalpha in regulation of myeloperoxidase expression in irradiated HL60 promyelocytic cells. Biochim Biophys Acta, 2000, 1495(3):237–249

    Article  CAS  PubMed  Google Scholar 

  16. Brännström J, Hässler S, Peltonen L, et al. Defect internalization and tyrosine kinase activation in Aire deficient antigen presenting cells exposed to Candida albicans antigens. Clin Immunol, 2006, 121(3):265–273

    Article  PubMed  Google Scholar 

  17. Johnnidis JB, Venanzi ES, Taxman DJ, et al. Chromosomal clustering of genes controlled by the aire transcription factor. Proc Natl Acad Sci USA, 2005, 102(20):7233–7238

    Article  CAS  PubMed  Google Scholar 

  18. Devitt A, Moffatt OD, Raykundalia C, et al. Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature, 1998, 392(6675):505–509

    Article  CAS  PubMed  Google Scholar 

  19. Gumienny TL, Hengartner MO. How the worm removes corpses: the nematode C. elegans as a model system to study engulfment. Cell Death Differ, 2001, 8(6):564–568

    Article  CAS  PubMed  Google Scholar 

  20. Mangahas PM, Zhou Z. Clearance of apoptotic cells in Caenorhabditis elegans. Semin Cell Dev Biol, 2005, 16(2): 295–306

    Article  CAS  PubMed  Google Scholar 

  21. Su HP, Nakada-Tsukui K, Tosello-Trampont AC, et al. 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, 277(14):11 772–11 779

    Article  CAS  Google Scholar 

  22. Wu YC, Horvitz HR. The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC transporters. Cell, 1998, 93(6):951–960

    Article  CAS  PubMed  Google Scholar 

  23. Wu YC, Tsai MC, Cheng LC, et al. C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pathway to control cell migration and cell corpse engulfment. Dev Cell, 2001, 1(4):491–502

    Article  CAS  PubMed  Google Scholar 

  24. Reddien PW, Horvitz HR. CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans. Nat Cell Biol, 2000, 2(3):131–136

    Article  CAS  PubMed  Google Scholar 

  25. Gumienny TL, Brugnera E, Tosello-Trampont AC, et al. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell, 2001, 107(1):27–41

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Liang Shi  (石 亮), Lihua Hu  (胡丽华) & Yirong Li  (李一荣)

Authors
  1. Liang Shi  (石 亮)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lihua Hu  (胡丽华)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yirong Li  (李一荣)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lihua Hu  (胡丽华).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shi, L., Hu, L. & Li, Y. Upregulation of phagocytic clearance of apoptotic cells by autoimmune regulator. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 30, 145–148 (2010). https://doi.org/10.1007/s11596-010-0202-5

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-010-0202-5

Key words

Search

Navigation