title: Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion.
abstract: Myeloid-related proteins (MRPs) 8 and 14 are cytosolic proteins secreted from myeloid cells as proinflammatory mediators. Currently, the functional role of circulating extracellular MRP8/14 is unclear. Our present study identifies extracellular MRP8/14 as an autocrine player in the leukocyte adhesion cascade. We show that E-selectin-PSGL-1 interaction during neutrophil rolling triggers Mrp8/14 secretion. Released MRP8/14 in turn activates a TLR4-mediated, Rap1-GTPase-dependent pathway of rapid β2 integrin activation in neutrophils. This extracellular activation loop reduces leukocyte rolling velocity and stimulates adhesion. Thus, we identify Mrp8/14 and TLR4 as important modulators of the leukocyte recruitment cascade during inflammation in vivo.
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Pruenster
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Angela R M
authors.initials: AR
authors.lastname: Kurz
authors.affiliation: Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Chung
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Xiao
authors.initials: X
authors.lastname: Cao-Ehlker
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bieber
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Nussbaum
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Bierschenk
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Tanja K
authors.initials: TK
authors.lastname: Eggersmann
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Rohwedder
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Heinig
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Immler
authors.affiliation: Department of Molecular Medicine, Max Planck Institute for Biochemistry, Martinsried, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Moser
authors.affiliation: Department of Neuroinflammation, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Koedel
authors.affiliation: Institute of Immunology, University of Muenster, Muenster, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gran
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: Max Planck Institute for Biomolecular Medicine, Münster, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität, Munich, Germany.
authors.forename: Admar
authors.initials: A
authors.lastname: Verschoor
authors.affiliation: Immunology Group, University of Lund, Lund, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Leanderson
authors.affiliation: Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.affiliation: Institute of Immunology, University of Muenster, Muenster, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.affiliation: Institute of Immunology, University of Muenster, Muenster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.affiliation: Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Markus
authors.identifier: 0000000276893613
authors.initials: M
authors.lastname: Sperandio
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism*; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism*; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D005786:Gene Expression Regulation; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D036904:Leukocyte Rolling / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D011485:Protein Binding
chemical_list: D018821:CD18 Antigens; D040501:Calgranulin A; D040502:Calgranulin B; D018960:Hyaluronan Receptors; C576329:S100A9 protein, mouse; C086145:S100a8 protein, mouse