title: Platelets Guide Leukocytes to Their Sites of Extravasation.
abstract: Effective immune responses require the directed migration of leukocytes from the vasculature to the site of injury or infection. How immune cells "find" their site of extravasation remains largely obscure. Here, we identified a previously unrecognized role of platelets as pathfinders guiding leukocytes to their exit points in the microvasculature: upon onset of inflammation, circulating platelets were found to immediately adhere at distinct sites in venular microvessels enabling these cellular blood components to capture neutrophils and, in turn, inflammatory monocytes via CD40-CD40L-dependent interactions. In this cellular crosstalk, ligation of PSGL-1 by P-selectin leads to ERK1/2 MAPK-dependent conformational changes of leukocyte integrins, which promote the successive extravasation of neutrophils and monocytes to the perivascular tissue. Conversely, blockade of this cellular partnership resulted in misguided, inefficient leukocyte responses. Our experimental data uncover a platelet-directed, spatiotemporally organized, multicellular crosstalk that is essential for effective trafficking of leukocytes to the site of inflammation.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Klinikum der Universität München, Munich, Germany.|Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Munich, Germany.
authors.forename: Gabriele
authors.identifier: 0000-0003-2448-9210
authors.initials: G
authors.lastname: Zuchtriegel
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Munich, Germany.
authors.forename: Bernd
authors.identifier: 0000-0002-2615-0803
authors.initials: B
authors.lastname: Uhl
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Puhr-Westerheide
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Munich, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Pörnbacher
authors.affiliation: Department of Radiation Oncology, Klinikum der Universität München, Munich, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Munich, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Krombach
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Klinikum der Universität München, Munich, Germany.|Walter Brendel Centre of Experimental Medicine, Klinikum der Universität München, Munich, Germany.
authors.forename: Christoph Andreas
authors.initials: CA
authors.lastname: Reichel
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D016023:Integrins / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D019007:P-Selectin / Q000378:metabolism; D014657:Vasculitis / Q000378:metabolism* / Q000473:pathology
chemical_list: D019013:CD40 Antigens; D016023:Integrins; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019041:L-Selectin; D023201:CD40 Ligand