title: Crucial role of Plexin C1 for pulmonary inflammation and survival during lung injury.
abstract: Acute pulmonary inflammation during lung injury is initiated by the migration of neutrophils into the alveolar space. The severity of these inflammatory changes within the pulmonary tissue determines the severity of lung injury and ultimately patient outcome. Recent work has demonstrated that the guidance protein Semaphorin 7A propagates the infiltration of neutrophils into an hypoxic tissue site, yet the role of its target receptor Plexin C1 (PLXNC1) during lung injury is to date unknown. We demonstrate here that PLXNC1(+) neutrophils are present within the alveolar space and that PLXNC1 is induced in vitro and in vivo during lung injury. In a model of high-pressure ventilation PLXNC1(-/-) animals show decreased signs of alveolar inflammation and improved survival compared with wild-type controls. Studies employing chimeric animals identified the hematopoietic expression of PLXNC1 to be of crucial importance for the observed results. Functional inhibition of PLXNC1 resulted in improved survival and ameliorated the signs of inflammation within the lung. Furthermore, the injection of a peptide binding to PLXNC1 resulted in improved survival and attenuated pulmonary inflammation. As such we demonstrate here, that previously unknown PLXNC1 holds significant importance for degree of pulmonary inflammation and determines outcome during experimental lung injury.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital; Eberhard-Karls University, Tübingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Granja
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital; Eberhard-Karls University, Tübingen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Köhler
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital; Eberhard-Karls University, Tübingen, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Mirakaj
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: E
authors.initials: E
authors.lastname: Nelson
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital; Eberhard-Karls University, Tübingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: König
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital; Eberhard-Karls University, Tübingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Rosenberger
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011014:Pneumonia / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics*; D039961:Semaphorins / Q000737:chemistry / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; C492112:Plxna3 protein, mouse; D011956:Receptors, Cell Surface; C118753:SEMA7A protein, human; D039961:Semaphorins