title: Heparin can liberate high molecular weight DNA from secondary necrotic cells.
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.
authors.affiliation: Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. gbarna@korb1.sote.hu
authors.forename: Gábor
authors.initials: G
authors.lastname: Barna
authors.forename: Anna
authors.initials: A
authors.lastname: Sebestyén
authors.forename: Zsuzsanna A
authors.initials: ZA
authors.lastname: Dunai
authors.forename: Balázs
authors.initials: B
authors.lastname: Csernus
authors.forename: Rudolf
authors.initials: R
authors.lastname: Mihalik
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D002460:Cell Line; D004247:DNA / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects*; D017313:Fenretinide / Q000009:adverse effects*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D009336:Necrosis / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics; D011419:Propidium / Q000009:adverse effects; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D015842:Serine Proteinase Inhibitors; C484771:benzyloxycarbonyl-valyl-aspartic acid fluoromethyl ketone; D017313:Fenretinide; D011419:Propidium; D006493:Heparin; D004247:DNA