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.
Keywords: adaptive immunity; inflammation; interleukin-10; killer cells, natural; myocardial infarction.