title: Onset of Inflammation With Ischemia: Implications for Donor Lung Preservation and Transplant Survival.
abstract: Lungs stored ahead of transplant surgery experience ischemia. Pulmonary ischemia differs from ischemia in the systemic organs in that stop of blood flow in the lung leads to loss of shear alone because the lung parenchyma does not rely on blood flow for its cellular oxygen requirements. Our earlier studies on the ischemia-induced mechanosignaling cascade showed that the pulmonary endothelium responds to stop of flow by production of reactive oxygen species (ROS). We hypothesized that ROS produced in this way led to induction of proinflammatory mediators. In this study, we used lungs or cells subjected to various periods of storage and evaluated the induction of several proinflammatory mediators. Isolated murine, porcine and human lungs in situ showed increased expression of cellular adhesion molecules; the damage-associated molecular pattern protein high-mobility group box 1 and the corresponding pattern recognition receptor, called the receptor for advanced glycation end products; and induction stabilization and translocation of hypoxia-inducible factor 1α and its downstream effector VEGFA, all of which are participants in inflammation. We concluded that signaling with lung preservation drives expression of inflammatory mediators that potentially predispose the donor lung to an inflammatory response after transplant.
authors.affiliation: Institute for Environmental Medicine and Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: J-Q
authors.initials: JQ
authors.lastname: Tao
authors.affiliation: Institute for Environmental Medicine and Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: E M
authors.initials: EM
authors.lastname: Sorokina
authors.affiliation: Institute for Environmental Medicine and Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: J P
authors.initials: JP
authors.lastname: Vazquez Medina
authors.affiliation: Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors.forename: M K
authors.initials: MK
authors.lastname: Mishra
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY.
authors.forename: J
authors.initials: J
authors.lastname: Satalin
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY.
authors.forename: G F
authors.initials: GF
authors.lastname: Nieman
authors.affiliation: Cardiovascular Surgery Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: J R
authors.initials: JR
authors.lastname: Nellen
authors.affiliation: Cardiovascular Surgery Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: B
authors.initials: B
authors.lastname: Beduhn
authors.affiliation: Cardiovascular Surgery Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: E
authors.initials: E
authors.lastname: Cantu
authors.affiliation: Surgical Critical Care, University of Maryland Medical Center, Baltimore, MD.
authors.forename: N M
authors.initials: NM
authors.lastname: Habashi
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Jungraithmayr
authors.affiliation: Cardiovascular Surgery Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.|Pulmonary Allergy and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: J D
authors.initials: JD
authors.lastname: Christie
authors.affiliation: Institute for Environmental Medicine and Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: S
authors.identifier: 0000-0002-1365-5167
authors.initials: S
authors.lastname: Chatterjee
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000453:epidemiology*; D018836:Inflammation Mediators / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008168:Lung / Q000503:physiopathology*; D016040:Lung Transplantation; D051379:Mice; D009926:Organ Preservation / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014019:Tissue Donors
chemical_list: D018836:Inflammation Mediators; D017382:Reactive Oxygen Species
keywords: adhesion molecules/integrins; basic (laboratory) research/science; lung transplantation/pulmonology; signaling/signaling pathways; translational research/science