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Blood, 5 November 2009, Vol. 114, No. 19, pp. 4209-4220. Prepublished online as a Blood First Edition Paper on July 28, 2009; DOI 10.1182/blood-2009-02-206169. This Article Full Text Full Text (PDF) Supplemental Methods, Figures, and Videos All Versions of this Article: blood-2009-02-206169v1 114/19/4209    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Schymeinsky, J. Articles by Walzog, B. PubMed PubMed Citation Articles by Schymeinsky, J. Articles by Walzog, B. Related Collections Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS A fundamental role of mAbp1 in neutrophils: impact on β2 integrin–mediated phagocytosis and adhesion in vivo Jürgen Schymeinsky1,*, Ronald Gerstl1,*, Ingrid Mannigel1, Katy Niedung1, David Frommhold2, Klaus Panthel3, Jürgen Heesemann3, Michael Sixt4, Thomas Quast5, Waldemar Kolanus5, Attila Mocsai6, Jürgen Wienands7, Markus Sperandio1, and Barbara Walzog1 1 Walter Brendel Centre for Experimental Medicine, Ludwig-Maximilians-University Munich, Munich, Germany; 2 Department of Neonatology, Children's Hospital, University of Heidelberg, Heidelberg, Germany; 3 Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University Munich, Munich, Germany; 4 Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany; 5 LIMES Institute (Life and Medical Sciences Bonn) Program Unit Molecular Immune and Cell Biology, Laboratory of Molecular Immunology, University of Bonn, Bonn, Germany; 6 Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary; and 7 Institute of Cellular and Molecular Immunology, Georg-August-University of Göttingen, Göttingen, Germany The mammalian actin-binding protein 1 (mAbp1, Hip-55, SH3P7) is phosphorylated by the nonreceptor tyrosine kinase Syk that has a fundamental effect for several β2 integrin (CD11/CD18)–mediated neutrophil functions. Live cell imaging showed a dynamic enrichment of enhanced green fluorescence protein–tagged mAbp1 at the phagocytic cup of neutrophil-like differentiated HL-60 cells during β2 integrin–mediated phagocytosis of serum-opsonized Escherichia coli. The genetic absence of Syk or its pharmacologic inhibition using piceatannol abrogated the proper localization of mAbp1 at the phagocytic cup. The genetic absence or down-regulation of mAbp1 using the RNA interference technique significantly compromised β2 integrin–mediated phagocytosis of serum-opsonized E coli or Salmonella typhimurium in vitro as well as clearance of S typhimurium infection in vivo. Moreover, the genetic absence of mAbp1 almost completely abrogated firm neutrophil adhesion under physiologic shear stress conditions in vitro as well as leukocyte adhesion and extravasation in inflamed cremaster muscle venules of mice treated with tumor-necrosis factor . Functional analysis showed that the down-regulation of mAbp1 diminished the number of β2 integrin clusters in the high-affinity conformation under flow conditions. These unanticipated results define mAbp1 as a novel molecular player in integrin biology that is critical for phagocytosis and firm neutrophil adhesion under flow conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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