Integrative Physiology Methods and Results: Depletion of Nk Cells from Mice Had Little Effect on Cytokine Expression (tumor Necrosis Lung Natural Killer Cells Play a Major Counter-regulatory Role in Pulmonary Vascular Hyperpermeability after Myocardial Infarction

L eft ventricular (LV) remodeling after myocardial infarc-tion (MI) results in LV dilation, a major cause of conges-tive heart failure and sudden cardiac death. MI causes sterile inflammation, which is characterized by the recruitment and activation of immune cells of the innate and adaptive immune systems. These cells are likely to have cell type–specific functions in the time-course after MI that involves clearance of dead tissues, the reparative response, and adverse remodeling. Disruption of myeloperoxidase (MPO), released predominantly by neutrophils, decreases leukocyte infiltration and LV dilation, enhances ventricular function, and delays early death attributable to myocardial rupture, 4 whereas macrophage depletion impairs wound healing and increases LV remodel-ing after MI. Dendritic cells are a potent immunoprotective regulator during the postinfarction healing process via their control of monocyte/macrophage homeostasis. 6 Treg cells serve to protect against adverse ventricular remodeling and contribute to improved cardiac function after MI via inhibition of inflammation and direct protection of cardiomyocytes. 7 γδT cells are the major source of interleukin (IL)-17 in the infarcted myocardium and function specifically in the late re-modeling stages by promoting sustained infiltration of neutro-phils and macrophages, stimulating macrophages to produce proinflammatory cytokines, aggravating cardiomyocyte death, and enhancing fibroblast proliferation and profibrotic gene expression via IL-17 production. 3 Natural killer (NK) cells (belonging to the group of innate lymphoid cells) are defined as large granular lymphocytes and constitute the third kind of cells differentiated from the common lymphoid progenitor generating B and T cells. 8 NK cells differ from NK T cells (NKT) phenotypically, by origin, and 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. 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 …