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Pro‐apoptosis effects of neutrophils in mice subjected to myocardial ischemic reperfusion in vivo
Author(s) -
Wang XiaoLiang,
Tao Lin,
Zhao RongRui,
Ma Xin L.,
Liu HuiRong
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1154-b
Subject(s) - apoptosis , myeloperoxidase , nitrotyrosine , in vivo , chemistry , medicine , inflammation , reperfusion injury , nitric oxide , pharmacology , endocrinology , ischemia , nitric oxide synthase , biology , biochemistry , microbiology and biotechnology
Aim To determine potential mechanisms involved in PMNs′ contribution to myocardial ischemic reperfusion (MI/R). Method 32 male adult mice were randomly divided into equal four groups: Vehicle, 1400W(iNOS inhibitor), Anti‐PMNs (anti‐PMN serum, i.p., 30μl/day for 3 consecutive days prior to MI/R) and Sham group. MI/R was produced by ligating the LAD for 30min followed by 5 hours of reperfusion. Myocardial apoptotic index, caspase3, MPO activity and ONOO − formation (measured by nitrotyrosine, NT) were determined. Result 1. Compared with sham group MI/R markedly increased apoptotic index (1.02±0.16% vs. 18.01±0.06%, P <0.01), caspase3 activity (63.82±8.40 vs. 25.64±2.60μM/mg, P <0.001), MPO activity (163.31±12.95 vs. 65.52±7.66ng/mg, P <0.001) and NT content (6.8±0.67 vs.1.6±0.14nmol/g, P <0.001); 2. Both Anti‐PMNs and 1400W treatment reduced reperfusion‐induced apoptotic index, caspase3 activity and NT content; MPO activity in Anti‐PMNs group was 84.52±9.62ng/mg ( P <0.001 vs. vehicle); 3. As for the reduction of apoptosis and the formation of NT, there were no significant differences between Anti‐PMNs and 1400W group, but the MPO activity in 1400W group was much higher ( P <0.005). Conclusion PMNs contribute to MI/R‐induced apoptosis by increasing iNOS, subsequent production of ONOO − and activating pro‐apoptotic signaling pathways. Anti‐PMNs treatment may not only attenuate postischemic myocardial inflammation as previously reported, but may also protect the heart from subsequent MI/R‐induced apoptosis.