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DAP12 expression in lung macrophages mediates ischemia/reperfusion injury by promoting neutrophil extravasation.
Spahn, Jessica H; Li, Wenjun; Bribriesco, Alejandro C; Liu, Jie; Shen, Hua; Ibricevic, Aida; Pan, Jie-Hong; Zinselmeyer, Bernd H; Brody, Steven L; Goldstein, Daniel R; Krupnick, Alexander S; Gelman, Andrew E; Miller, Mark J; Kreisel, Daniel.
Afiliación
  • Spahn JH; Department of Surgery, Washington University, St. Louis, MO 63110;
  • Li W; Department of Surgery, Washington University, St. Louis, MO 63110;
  • Bribriesco AC; Department of Surgery, Washington University, St. Louis, MO 63110;
  • Liu J; Department of Surgery, Washington University, St. Louis, MO 63110;
  • Shen H; Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510;
  • Ibricevic A; Department of Medicine, Washington University, St. Louis, MO 63110; and.
  • Pan JH; Department of Medicine, Washington University, St. Louis, MO 63110; and.
  • Zinselmeyer BH; Department of Pathology & Immunology, Washington University, St. Louis, MO 63110.
  • Brody SL; Department of Medicine, Washington University, St. Louis, MO 63110; and.
  • Goldstein DR; Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510;
  • Krupnick AS; Department of Surgery, Washington University, St. Louis, MO 63110;
  • Gelman AE; Department of Surgery, Washington University, St. Louis, MO 63110; Department of Pathology & Immunology, Washington University, St. Louis, MO 63110.
  • Miller MJ; Department of Medicine, Washington University, St. Louis, MO 63110; and.
  • Kreisel D; Department of Surgery, Washington University, St. Louis, MO 63110; Department of Pathology & Immunology, Washington University, St. Louis, MO 63110 kreiseld@wudosis.wustl.edu.
J Immunol ; 194(8): 4039-48, 2015 Apr 15.
Article en En | MEDLINE | ID: mdl-25762783
Neutrophils are critical mediators of innate immune responses and contribute to tissue injury. However, immune pathways that regulate neutrophil recruitment to injured tissues during noninfectious inflammation remain poorly understood. DAP12 is a cell membrane-associated protein that is expressed in myeloid cells and can either augment or dampen innate inflammatory responses during infections. To elucidate the role of DAP12 in pulmonary ischemia/reperfusion injury (IRI), we took advantage of a clinically relevant mouse model of transplant-mediated lung IRI. This technique allowed us to dissect the importance of DAP12 in tissue-resident cells and those that infiltrate injured tissue from the periphery during noninfectious inflammation. Macrophages in both mouse and human lungs that have been subjected to cold ischemic storage express DAP12. We found that donor, but not recipient, deficiency in DAP12 protected against pulmonary IRI. Analysis of the immune response showed that DAP12 promotes the survival of tissue-resident alveolar macrophages and contributes to local production of neutrophil chemoattractants. Intravital imaging demonstrated a transendothelial migration defect into DAP12-deficient lungs, which can be rescued by local administration of the neutrophil chemokine CXCL2. We have uncovered a previously unrecognized role for DAP12 expression in tissue-resident alveolar macrophages in mediating acute noninfectious tissue injury through regulation of neutrophil trafficking.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Trasplante de Pulmón / Macrófagos Alveolares / Infiltración Neutrófila / Proteínas Adaptadoras Transductoras de Señales / Disfunción Primaria del Injerto / Pulmón / Neutrófilos Límite: Animals / Humans Idioma: En Revista: J Immunol Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Trasplante de Pulmón / Macrófagos Alveolares / Infiltración Neutrófila / Proteínas Adaptadoras Transductoras de Señales / Disfunción Primaria del Injerto / Pulmón / Neutrófilos Límite: Animals / Humans Idioma: En Revista: J Immunol Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos