Lung natural killer cells play a major counter-regulatory role in pulmonary vascular hyperpermeability after myocardial infarction

Xiaoxiang Yan, Ahmed E. Hegab, Jin Endo, Atsushi Anzai, Tomohiro Matsuhashi, Yoshinori Katsumata, Kentaro Ito, Tsunehisa Yamamoto, Tomoko Betsuyaku, Ken Shinmura, Weifeng Shen, Eric Vivier, Keiichi Fukuda, Motoaki Sano

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


RATIONALE:: Natural killer (NK) cells are lymphocytes of the innate immune system that play specialized and niche-specific roles in distinct organs. OBJECTIVE:: We investigated the possible function of NK cells in the pathogenesis of congestive heart failure after myocardial infarction. METHODS AND RESULTS:: Depletion of NK cells from mice had little effect on cytokine expression (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β), neutrophil and macrophage infiltration into infarcted myocardium, or left ventricular remodeling after myocardial infarction. However, these mice exhibited severe respiratory distress associated with protein-rich, high-permeability alveolar edema accompanied by neutrophil infiltration. In addition, there were 20-fold more NK cells in the mouse lungs than in heart, and these cells were accumulated around the vasculature. CD107a-positive and interferon-γ-positive cell populations were unchanged, whereas IL-10-positive populations increased. Adoptive transfer of NK cells from wild-type mice, but not from IL-10 knockout mice, into the NK cell-depleted mice rescued the respiratory phenotype. IL-1β-mediated dextran leakage from a lung endothelial cell monolayer was also blocked by coculture with NK cells from wild-type mice but not from IL-10 knockout mice. CONCLUSIONS:: This study is the first to identify a critical role for lung NK cells in protecting lung from the development of cardiogenic pulmonary edema after myocardial infarction.

Original languageEnglish
Pages (from-to)637-649
Number of pages13
JournalCirculation research
Issue number4
Publication statusPublished - 2014 Feb 14


  • adaptive immunity
  • inflammation
  • interleukin-10
  • killer cells, natural
  • myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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