A fundamental role of mAbp1 in neutrophils: Impact on β2 integrin-mediated phagocytosis and adhesion in vivo

Jürgen Schymeinsky, Ronald Gerstl, Ingrid Mannigel, Katy Niedung, David Frommhold, Klaus Panthel, Jürgen Heesemann, Michael Sixt, Thomas Quast, Waldemar Kolanus, Attila Mocsai, Jürgen Wienands, Markus Sperandio, Barbara Walzog

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Abstract

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 ofmAbp1using theRNA 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 α. 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.

Original languageEnglish
Pages (from-to)4209-4220
Number of pages12
JournalBlood
Volume114
Issue number19
DOIs
Publication statusPublished - Nov 5 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Schymeinsky, J., Gerstl, R., Mannigel, I., Niedung, K., Frommhold, D., Panthel, K., Heesemann, J., Sixt, M., Quast, T., Kolanus, W., Mocsai, A., Wienands, J., Sperandio, M., & Walzog, B. (2009). A fundamental role of mAbp1 in neutrophils: Impact on β2 integrin-mediated phagocytosis and adhesion in vivo. Blood, 114(19), 4209-4220. https://doi.org/10.1182/blood-2009-02-206169