the axonal guidance receptor neogenin promotes acute inflammation轴突引导受体neogenin促进急性炎症.pdfVIP

The Axonal Guidance Receptor Neogenin Promotes Acute Inflammation ¨ 1,2 1 1,2 1,2 1 Klemens Konig , Dimitra Gatidou , Tiago Granja , Jens Meier , Peter Rosenberger *, Valbona Mirakaj1* ¨ ¨ ¨ 1 Department of Anesthesiology and Intensive Care Medicine, Tubingen University Hospital, Eberhard-Karls University Tubingen, Tubingen, Germany, 2 Clinic of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt am Main, Johann Wolfgang Goethe University, Frankfurt am Main, Germany Abstract Neuronal guidance proteins (NGP) were originally described in the context of axonal growth and migration. Yet recent work has demonstrated that NGPs also serve as guidance cues for immune competent cells. A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown. We report here that neogenin is abundantly expressed outside the nervous system and that animals with endogenous repression of neogenin (Neo12/ 2) demonstrate attenuated changes of acute inflammation. Studies using functional inhibition of neogenin resulted in a significant attenuation of inflammatory peritonitis. In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo12/ 2 to be responsible for the attenuated inflammatory response. Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response an