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Ox-LDL can enhance the interaction of mice natural killer cells and dendritic cells via the CD48-2B4 pathway

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Abstract

The importance of the interaction between natural killer (NK) cells and dendritic cells (DCs) in the expansion of antiviral and antitumor immune responses is well documented; however, limited information on NK/DC interaction during atherosclerosis is available. Inflammation plays an important role in the development of atherosclerosis, and oxidized low-density lipoprotein (ox-LDL) is believed to play a critical role in the development and progression of atherosclerosis. In this study, we developed a NK/DC coculture system to examine the role of ox-LDL in modulating the interaction of mice NK cells and DCs. Fresh NK cells were cocultured with DCs in the absence or presence of ox-LDL. We examined the cytokines released during the interaction. This report provides the first evidence of an enhancement effect by ox-LDL on the NK/DC crosstalk. Notably, we found that ox-LDL significantly promoted the interaction of NK cells and DCs via CD48-2B4 contact-dependent mechanisms. These findings highlight the importance of NK/DCs crosstalk in atherosclerosis and provide new information about the possible mechanisms of atherosclerosis.

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References

  1. Hansson GK, Libby P (2006) The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 6:508–519

    Article  PubMed  CAS  Google Scholar 

  2. Bobryshev YV (2005) Identification of natural killer cells in human atherosclerotic plaque. Atherosclerosis 180:423–427

    Article  PubMed  CAS  Google Scholar 

  3. Hjerpe C, Johansson D, Hermansson A, Hansson GK (2010) Dendritic cells pulsed with malondialdehyde modified low density lipoprotein aggravate atherosclerosis in Apoe(−/−) mice. Atherosclerosis 209:436–441

    Article  PubMed  CAS  Google Scholar 

  4. Habets KLL, van Puijvelde GHM, van Duivenvoorde LM (2010) Vaccination using oxidized low-density lipoprotein-pulsed dendritic cells reduces atherosclerosis in LDL receptor-deficient mice. Cardiovasc Res 85:622–630

    Article  PubMed  CAS  Google Scholar 

  5. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811

    Article  PubMed  CAS  Google Scholar 

  6. Hansson GK, Libby P, Schonbeck U (2002) Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 91:281–291

    Article  PubMed  CAS  Google Scholar 

  7. Curtiss LK, Kubo N, Schiller NK, Boisvert WA (2000) Participation of innate and acquired immunity in atherosclerosis. Immunol Res 21:167–176

    Article  PubMed  CAS  Google Scholar 

  8. Yao HC, Liu SQ, Yu K (2009) Interleukin-2 enhances the cytotoxic activity of circulating natural killer cells in patients with chronic heart failure. Heart Vessels 24:283–286

    Article  PubMed  Google Scholar 

  9. Trinchieri G (1998) Biology of natural killer cells. Adv Immunol 47:187

    Article  Google Scholar 

  10. Raulet DH (2004) Interplay of natural killer cells and their receptors with the adaptive immune response. Nat Immunol 5:996

    Article  PubMed  CAS  Google Scholar 

  11. Cooper MA, Fehniger TA, Fuchs A, Colonna M, Caligiuri MA (2004) NK cell and DC interactions. Trends Immunol 25:47

    Article  PubMed  CAS  Google Scholar 

  12. Lee KM, Bhawan S, Majima T (2003) Cutting edge: the NK cell receptor 2B4 augments antigen-specific T cell cytotoxicity through CD48 ligation on neighboring T cells. J Immunol 170:4881

    PubMed  CAS  Google Scholar 

  13. Sousa CR, Hieny S, Scharton-Kersten T, Jankovic D, Charest H (1997) In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas. J Exp Med 186:1819

    Article  Google Scholar 

  14. Gerosa F, Baldani-Guerra B, Nisii C, Marchesini V, Carra G (2002) Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med 195:327–333

    Article  PubMed  CAS  Google Scholar 

  15. Ferlazzo G, Munz C (2004) NK cell compartments and their activation by dendritic cells. J Immunol 172:1333–1339

    PubMed  CAS  Google Scholar 

  16. Borg C, Jalil A, Laderach D (2004) NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs. Blood 104:3267–3275

    Article  PubMed  CAS  Google Scholar 

  17. Osada T (2001) Peripheral blood dendritic cells, but not monocyte-derived dendritic cells, can augment human NK cell function. Cell Immunol 213:14–23

    Article  PubMed  CAS  Google Scholar 

  18. Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146

    Article  PubMed  CAS  Google Scholar 

  19. Piccioli D, Sbrana S, Melandri E, Valiante NM (2002) Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells. J Exp Med 195:335–341

    Article  PubMed  CAS  Google Scholar 

  20. Lee KM, Forman JP, McNerney ME, Stepp S (2005) Requirement of homotypic NK cell interactions through 2B4 (CD244)/CD48 in the generation of NK effector functions. Blood 10:1182

    Google Scholar 

  21. Assarsson E, Kambayashi T, Persson CM, Ljunggren HG (2005) 2B4 co-stimulation: NK cells and their control of adaptive immune responses. Mol Immunol 42:419–423

    Article  PubMed  CAS  Google Scholar 

  22. Nakajima H, Cella M, Langen H, Friedlein A, Colonna M (1999) Activating interactions in human NK cell recognition: the role of 2B4–CD48. Eur J Immunol 29:1676–1683

    Article  PubMed  CAS  Google Scholar 

  23. Fernandez-Real JM, Ricart W (2003) Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24:278–301

    Article  PubMed  CAS  Google Scholar 

  24. Crisby M, Kublickiene K, Henareh L (2009) Circulating levels of autoantibodies to oxidized low-density lipoprotein and C-reactive protein levels correlate with endothelial function in resistance arteries in men with coronary heart disease. Heart Vessels 24:90–95

    Article  PubMed  Google Scholar 

  25. Whitman SC, Rateri DL, Szilvassy SJ (2004) Depletion of natural killer cell function decreases atherosclerosis in low-density lipoprotein receptor null mice. Arterioscler Thromb Vasc Biol 24:1049–1054

    Article  PubMed  CAS  Google Scholar 

  26. Trinchieri G (1989) Biology of NK cells. Adv Immunol 47:187–376

    Article  PubMed  CAS  Google Scholar 

  27. Perussia B (1991) Lymphokine-activated killer cells, natural killer cells and cytokines. Curr Opin Immunol 3:49

    Article  PubMed  CAS  Google Scholar 

  28. Biron CA, Byron KS, Sullivan JL (1989) Severe herpes virus infections in an adolescent without natural killer cells. N Engl J Med 320:1731–1735

    Article  PubMed  CAS  Google Scholar 

  29. Ruggeri L, Capanni M, Urbani E (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2029–2031

    Article  Google Scholar 

  30. Walzer T, Dalod M, Robbins SH (2005) Natural-killer cells and dendritic cells: “l’ union fait l force”. Blood 106:2252–2258

    Article  PubMed  CAS  Google Scholar 

  31. Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P (1999) Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med 5:405–411

    Article  PubMed  CAS  Google Scholar 

  32. Yu Y, Hagihara M, Ando K, Gansuvd B (2001) Enhancement of human cord blood CD34+ cell-derived NK cell cytotoxicity by dendritic cells. J Immunol 166:1590–1600

    PubMed  CAS  Google Scholar 

  33. Ferlazzo G, Pack M, Thomas D (2004) Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proc Natl Acad Sci USA 101:16606–16611

    Article  PubMed  CAS  Google Scholar 

  34. Moretta A (2002) Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat Rev Immunol 2:957–964

    Article  PubMed  CAS  Google Scholar 

  35. Loza MJ, Perussia B (2001) Final steps of natural killer cell maturation: a model for type 1-type 2 differentiation? Nat Immunol 2:917–924

    Article  PubMed  CAS  Google Scholar 

  36. Moretta A, Bottino C, Vitale M (2001) Activating receptors and co-receptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223

    Article  PubMed  CAS  Google Scholar 

  37. Moretta A (2000) Natural cytotoxicity receptors that trigger human NK-mediated cytolysis. Immunol Today 21:228–234

    Article  PubMed  CAS  Google Scholar 

  38. Marcenaro E (2003) CD59 is physically and functionally associated with natural cytotoxicity receptors and activates human NK cell-mediated cytotoxicity. Eur J Immunol 33:3367–3376

    Article  PubMed  CAS  Google Scholar 

  39. Shibuya A (1996) DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity 4:573–581

    Article  PubMed  CAS  Google Scholar 

  40. Flaig RM, Stark S, Waltzl C (2004) Cutting edge: NTB-A activates NK cells via homophilic interaction. J Immunol 172:6524–6527

    PubMed  CAS  Google Scholar 

  41. Kambayashi T, Assarsson E, Chambers BJ, Ljunggren HG (2001) Cutting edge: regulation of CD8(+) T cell proliferation by 2B4/CD48 interactions. J Immunol 167:6706–6710

    PubMed  CAS  Google Scholar 

  42. Assarsson E, Kambayashi T, Schatzle JD, Cramer SO, Jensen PE (2004) NK cells stimulate proliferation of T and NK cells through 2B4/CD48 interactions. J Immunol 173:174–180

    PubMed  CAS  Google Scholar 

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Acknowledgments

The project was supported by the Health Bureau of Zhejiang Province, China (grant no. 2008A075).

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Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79, Qingchun Road, Hangzhou, 310003, Zhejiang, China

    Kan Dong, Jun-Hua Ge, Shu-Lian Gu, Shan Li, Wei-Guo Zhu, Fang-Yan Fan & Jian-Hua Zhu

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  1. Kan Dong
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  2. Jun-Hua Ge
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  3. Shu-Lian Gu
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Correspondence to Jian-Hua Zhu.

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Dong, K., Ge, JH., Gu, SL. et al. Ox-LDL can enhance the interaction of mice natural killer cells and dendritic cells via the CD48-2B4 pathway. Heart Vessels 26, 637–645 (2011). https://doi.org/10.1007/s00380-010-0102-4

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