Effect of DNase I treatment and neutrophil depletion on acute limb ischemia-reperfusion injury in mice

Hassan Albadawi, Rahmi Oklu, Rita Elise Raacke Malley, Ryan M. O'Keefe, Thuy P. Uong, Nicholas R. Cormier, Michael T. Watkins

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Objective Extracellular traps (ETs) consisting of DNA-protein complexes formed after tissue injury contribute to the inflammatory and thrombosis cascades, thereby exacerbating injury. Exogenous DNase I has been suggested as a therapeutic strategy to limit injury in the brain and myocardium. These studies were designed to evaluate the effects of exogenous DNase I treatment on skeletal muscle injury after acute hindlimb ischemia-reperfusion (IR) injury in mice and to determine whether neutrophils are a major source of ETs in postischemic muscle tissue. Methods C57BL6 mice were subjected to 1.5 hours of tourniquet ischemia and 24 hours of reperfusion with and without human recombinant DNase I treatment. A separate set of mice was subjected to neutrophil depletion (ND), followed by the same intervals of IR. Laser Doppler imaging and tissue harvesting were done at 24 hours for assessment of limb perfusion, muscle fiber injury, adenosine triphosphate (ATP) level, markers of inflammation, thrombosis, and formation of ETs. Results DNase I treatment significantly reduced detection of ETs in postischemic muscle but did not alter skeletal muscle fiber injury, levels of proinflammatory molecules, or ATP level. DNase I treatment did enhance postischemic hindlimb perfusion, decreased infiltrating inflammatory cells, and reduced the expression of thrombin-antithrombin III. ND resulted in a significant yet small reduction in ETs in the postischemic muscle. ND did not alter skeletal muscle fiber injury, hindlimb perfusion, or ATP levels. Conclusions These data suggest that neither DNase I treatment nor ND was protective against IR injury, even though both decreased detection of ETs in skeletal muscle after IR. Neutrophils are not the only source of ETs after IR.

Original languageEnglish (US)
Pages (from-to)484-493
Number of pages10
JournalJournal of vascular surgery
Volume64
Issue number2
DOIs
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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