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Heparin can liberate high molecular weight DNA from secondary necrotic cells

Authors

  • Gábor Barna,

    Corresponding author
    1. Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, 1085 Budapest, Ülliő út 26, Hungary
      (email gbarna@korb1.sote.hu)
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  • Anna Sebestyén,

    1. Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, 1085 Budapest, Ülliő út 26, Hungary
    2. Tumour Progression Research Group-Joint Research Organization of the Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
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  • Zsuzsanna A. Dunai,

    1. Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, 1085 Budapest, Ülliő út 26, Hungary
    2. National Institute of Oncology, 1122 Budapest, Ráth Gy u 79, Hungary
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  • Balázs Csernus,

    1. Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, 1085 Budapest, Ülliő út 26, Hungary
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  • Rudolf Mihalik

    1. National Institute of Oncology, 1122 Budapest, Ráth Gy u 79, Hungary
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(email gbarna@korb1.sote.hu)

Abstract

The borderline between necrosis and apoptosis is indistinct, but that between types of cell death is important because necrosis may lead to local inflammation, whereas apoptosis usually does not. In certain autoimmune disorders, inhibition of cell death is crucial, since macromolecules released from the dead cells may accelerate the autoimmune processes. We have used various cell death inhibitors to block cell death induced by 4HPR [N-(4-hydroxyphenil)-retinamide] the BL41 and U937 cell lines. VD-FMK, a general caspase inhibitor, inhibited DNA fragmentation induced by 4HPR, but not PI (propidium iodide) uptake and necrosis. Interestingly heparin, a serine-protease inhibitor, lowered the PI fluorescence of the dead cell population and increased the sub-G1 population as measured by flow cytometry. Regarding these changes, we found that heparin failed to increase DNA fragmentation, but merely liberated high molecular mass DNA fragments from dead cells. The exact mechanism is unclear, but heparin during secondary necrosis might enter the cells, bind RNPs (ribonucleoproteins), and pull them out with the attached DNA, where they would be sensitive to enzymatic degradation. Thus, the results suggest that heparin treatment helps in the clearance of cell debris and decreases the immunogenity of secondary necrotic cells.

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