Loss of plasma membrane integrity, complement response and formation of reactive oxygen species during early myocardial ischemia/reperfusion

Mol Immunol. 2013 Dec;56(4):507-12. doi: 10.1016/j.molimm.2013.05.001. Epub 2013 Aug 1.

Abstract

Loss of plasma membrane integrity (LPMI) is a hallmark of necrotic cell death. The involvement of complement and ROS in the development of LPMI during the early stages of murine myocardial ischemia-reperfusion injury was investigated. LPMI developed within 1 h of reperfusion to a level that was sustained through 24 h. C3 deposition became significant at 3-h reperfusion and thus contributed little to LPMI prior to this time. SOD1 transgenic mice had significantly less LPMI compared with WT mice at 1 h of reperfusion but not at later time points. Catalase transgenic mice were not protected from LPMI at 1-h reperfusion compared with WT mice, but had 69% less LPMI at 3-h reperfusion. This protection was transient. At 24-h reperfusion the LPMI of catalase transgenic mice was identical to that of WT mice. The delayed benefits of over-expressed catalase compared with SOD1 are consistent with its antioxidant action downstream of SOD1. The onset of LPMI occurs within 1 h of reperfusion at a level that is maintained through 24 h. ROS contribute significantly to LPMI during the first 3 h of reperfusion, while complement deposition, which becomes significant after 3-h reperfusion, may contribute thereafter.

Keywords: Catalase; Complement; Inflammation; Loss of plasma membrane integrity (LPMI); Myocardial ischemia; Necrosis; Reactive oxygen species (ROS); Reperfusion injury; SOD1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Catalase / genetics
  • Catalase / metabolism*
  • Cell Membrane / metabolism*
  • Complement C3 / metabolism
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Time Factors

Substances

  • Complement C3
  • Reactive Oxygen Species
  • Catalase
  • Superoxide Dismutase