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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2016 (publ. 2015, arch)     Display Documents



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ID: 717274.0, MPI für molekulare Biomedizin / Jahrbuch 2016 (publ. 2015, arch)
Extracellular MRP8/14 is a regulator of beta2 integrin-dependent neutrophil slow rolling and adhesion
Authors:Pruenster, M.; Kurz, A. R.; Chung, K. J.; Cao-Ehlker, X.; Bieber, S.; Nussbaum, C. F.; Bierschenk, S.; Eggersmann, T. K.; Rohwedder, I.; Heinig, K.; Immler, R.; Moser, M.; Koedel, U.; Gran, S.; McEver, R. P.; Vestweber, D.; Verschoor, A.; Leanderson, T.; Chavakis, T.; Roth, J.; Vogl, T.; Sperandio, M.
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Nat Commun
Volume:6
Start Page:6915
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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 beta2 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.
Free Keywords:Animals; Antigens, CD18/genetics/*metabolism; Antigens, CD44/genetics/metabolism; Calgranulin A/genetics/*metabolism; Calgranulin B/genetics/*metabolism; Cell Adhesion/*physiology; Gene Expression Regulation; Inflammation/chemically induced/metabolism; Leukocyte Rolling/*physiology; Macrophages/physiology; Male; Mice; Mice, Knockout; Neutrophils/*physiology; Protein Binding
External Publication Status:published
Document Type:Article
Communicated by:Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Technische Universitat Dresden, Dresden, Germany. Department of Molecular Medicine, Max Planck Institute for Biochemistry, Martinsried, Germany. Department of Neuroinflammation, Ludwig-Maximilians Universitat, Munich, Germany. Institute of Immunology, University of Muenster, Muenster, Germany. Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. Max Planck Institute for Biomolecular Medicine, Munster, Germany. Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat, Munich, Germany. Immunology Group, University of Lund, Lund, Sweden.
Identifiers:ISSN:2041-1723 (Electronic) 2041-1723 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/25892652 [ID No:2]
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