title: Neutrophils scan for activated platelets to initiate inflammation.
abstract: Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. We report that neutrophil polarization within activated venules served to organize a protruding domain that engaged activated platelets present in the bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting in the redistribution of receptors that drive neutrophil migration. Consequently, neutrophils unable to polarize or to transduce signals through PSGL-1 displayed aberrant crawling, and blockade of this domain protected mice against thromboinflammatory injury. These results reveal that recruited neutrophils scan for activated platelets, and they suggest that the neutrophils' bipolarity allows the integration of signals present at both the endothelium and the circulation before inflammation proceeds.
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Vinatha
authors.initials: V
authors.lastname: Sreeramkumar
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Adrover
authors.affiliation: Unidad de Investigación Neurovascular, Department of Pharmacology, Faculty of Medicine, Universidad Complutense and Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ballesteros
authors.affiliation: Unidad de Investigación Neurovascular, Department of Pharmacology, Faculty of Medicine, Universidad Complutense and Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Cuartero
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Münster and Max Planck Institute Münster, Münster, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rossaint
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Izaskun
authors.initials: I
authors.lastname: Bilbao
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Nácher
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pitaval
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Irena
authors.initials: I
authors.lastname: Radovanovic
authors.affiliation: Division of Immunogenetics, Department of Immunobiology and Neuroscience, Kyushu University, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukui
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Rodger P
authors.initials: RP
authors.lastname: McEver
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Filippi
authors.affiliation: Unidad de Investigación Neurovascular, Department of Pharmacology, Faculty of Medicine, Universidad Complutense and Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lizasoain
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ruiz-Cabello
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Münster and Max Planck Institute Münster, Münster, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
authors.affiliation: Unidad de Investigación Neurovascular, Department of Pharmacology, Faculty of Medicine, Universidad Complutense and Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Moro
authors.affiliation: Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany. ahidalgo@cnic.es.
authors.forename: Andrés
authors.initials: A
authors.lastname: Hidalgo
mesh_terms: D000818:Animals; D001775:Blood Circulation; D001792:Blood Platelets / Q000276:immunology*; D002465:Cell Movement; D016764:Cell Polarity; D004730:Endothelium, Vascular / Q000276:immunology; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D015539:Platelet Activation; D015398:Signal Transduction; D013927:Thrombosis / Q000276:immunology*; D014699:Venules / Q000276:immunology
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein