title: Semaphorin 7A Aggravates Pulmonary Inflammation during Lung Injury.
abstract: The extent of pulmonary inflammation during lung injury ultimately determines patient outcome. Pulmonary inflammation is initiated by the migration of neutrophils into the alveolar space. Recent work has demonstrated that the guidance protein semaphorin 7A (SEMA7A) influences the migration of neutrophils into hypoxic tissue sites, yet, its role during lung injury is not well understood. Here, we report that the expression of SEMA7A is induced in vitro through pro-inflammatory cytokines. SEMA7A itself induces the production of pro-inflammatory cytokines in endothelial and epithelial cells, enhancing pulmonary inflammation. The induction of SEMA7A facilitates the transendothelial migration of neutrophils. In vivo, animals with deletion of SEMA7A expression showed reduced signs of pulmonary inflammatory changes following lipopolysaccharide challenge. We define here the role of SEMA7A in the development of lung injury and identify a potential pathway to interfere with these detrimental changes. Future anti-inflammatory strategies for the treatment of lung injury might be based on this finding.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany.
authors.forename: Judith Marlene
authors.initials: JM
authors.lastname: Roth
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Köhler
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany.
authors.forename: Mariella
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany.
authors.forename: Tiago Folgosa
authors.initials: TF
authors.lastname: Granja
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Rosenberger
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D045744:Cell Line, Tumor; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008070:Lipopolysaccharides / Q000378:metabolism; D055370:Lung Injury / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism* / Q000473:pathology; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D058851:GPI-Linked Proteins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C118753:SEMA7A protein, human; C485571:Sema7a protein, mouse; D039961:Semaphorins