A fundamental role of mAbp1 in neutrophils: impact on beta(2) integrin-mediated phagocytosis and adhesion in vivo
- Resource Type
- Authors
- Jürgen Wienands; Jürgen Schymeinsky; Ingrid Mannigel; Jürgen Heesemann; Ronald Gerstl; Attila Mócsai; Markus Sperandio; David Frommhold; Michael Sixt; Klaus Panthel; Waldemar Kolanus; Katy Niedung; Thomas Quast; Barbara Walzog
- Source
- Blood. 114(19)
- Subject
- Phagocytic cup
Salmonella typhimurium
Neutrophils
Phagocytosis
Immunology
Integrin
Syk
CD18
HL-60 Cells
Granulocyte
In Vitro Techniques
Biochemistry
src Homology Domains
03 medical and health sciences
Mice
0302 clinical medicine
medicine
Cell Adhesion
Escherichia coli
Animals
Humans
Syk Kinase
030304 developmental biology
Mice, Knockout
0303 health sciences
Mice, Inbred BALB C
biology
Cell adhesion molecule
Microfilament Proteins
Receptors, IgG
Intracellular Signaling Peptides and Proteins
Cell Biology
Hematology
Protein-Tyrosine Kinases
Mice, Mutant Strains
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
CD18 Antigens
biology.protein
RNA Interference
Tyrosine kinase
030215 immunology
- Language
- ISSN
- 1528-0020
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 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.