title: The plexin C1 receptor promotes acute inflammation.
abstract: Acute inflammation is the pathophysiological basis of important clinical conditions associated with organ failure. The initial inflammatory response is controlled by the chemokine system, yet recent data have indicated that the neuronal guidance cues are significantly involved in the orchestration of this process. Previous work has shown the proinflammatory capacity of the guidance cue semaphorin (Sema) 7a, but the role of one of its target receptors, the plexin C1 (PLXNC1) receptor is to date unknown. We report here that PLXNC1 is expressed outside the nervous system and induced during acute inflammation. PLXNC1(-/-) mice with C57BL/6 background demonstrated decreased inflammatory responses during zymosan A (ZyA)-induced peritonitis. Subsequent in vivo studies revealed altered rolling, adhesion, and transmigration properties of PLXNC1(-/-) leukocytes. Blockade of PLXNC1 was associated with attenuated chemotactic transendothelial migration properties in vitro. Studies in chimeric mice revealed that hematopoietic PLXNC1(-/-) animals demonstrated an attenuated inflammatory response. To probe the therapeutic potential of PLXNC1 we treated C57BL/6 WT mice with an anti-PLXNC1 antibody and a PLXNC1 binding peptide. Both of these interventions significantly dampened ZyA-induced peritonitis. These results implicate an important role of PLXNC1 during an acute inflammatory response and indicate PLXNC1 as a potential target for the control of conditions associated with acute inflammation.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Tübingen University Hospital, Eberhard-Karls University Tübingen, Tübingen, Germany; Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt am Main, Frankfurt, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: König
authors.forename: Linda
authors.initials: L
authors.lastname: Marth
authors.forename: Jan
authors.initials: J
authors.lastname: Roissant
authors.forename: Tiago
authors.initials: T
authors.lastname: Granja
authors.forename: Carla
authors.initials: C
authors.lastname: Jennewein
authors.forename: Vasudharani
authors.initials: V
authors.lastname: Devanathan
authors.forename: Mariella
authors.initials: M
authors.lastname: Schneider
authors.forename: David
authors.initials: D
authors.lastname: Köhler
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
authors.forename: Peter
authors.initials: P
authors.lastname: Rosenberger
mesh_terms: D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D039961:Semaphorins / Q000235:genetics / Q000276:immunology; D015054:Zymosan / Q000633:toxicity
chemical_list: D015703:Antigens, CD; D009419:Nerve Tissue Proteins; C492112:Plxna3 protein, mouse; D011956:Receptors, Cell Surface; C485571:Sema7a protein, mouse; D039961:Semaphorins; D015054:Zymosan
keywords: Inflammation; Neuronal Guidance Protein; Plexin C1; Semaphorin 7a