title: Lung natural killer cells play a major counter-regulatory role in pulmonary vascular hyperpermeability after myocardial infarction.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: From the Department of Cardiology, Rui Jin Hospital, Medical School of Jiaotong University, Shanghai, PR China (X.Y., W.S.); Departments of Cardiology (X.Y., J.E., A.A., T.M., Y.K., K.I., T.Y., K.F., M.S.), Pulmonary Medicine (A.E.H., T.B.), and Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, INSERM, Marseille, France (E.V.); Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Tokyo, Japan (M.S.).
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Yan
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Hegab
authors.forename: Jin
authors.initials: J
authors.lastname: Endo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Anzai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Katsumata
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ito
authors.forename: Tsunehisa
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Betsuyaku
authors.forename: Ken
authors.initials: K
authors.lastname: Shinmura
authors.forename: Weifeng
authors.initials: W
authors.lastname: Shen
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
authors.forename: Motoaki
authors.initials: M
authors.lastname: Sano
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002463:Cell Membrane Permeability / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011014:Pneumonia / Q000150:complications / Q000276:immunology* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000473:pathology; D011654:Pulmonary Edema / Q000150:complications / Q000276:immunology* / Q000473:pathology
chemical_list: C556062:IL10 protein, mouse; D053583:Interleukin-1beta; D016753:Interleukin-10; D049452:Green Fluorescent Proteins
keywords: adaptive immunity; inflammation; interleukin-10; killer cells, natural; myocardial infarction