Integrin beta 1 regulates phagosome maturation in macrophages through Rac expression.
Phagocytosis and subsequent phagosome maturation by professional phagocytes are essential in the clearance of infectious microbial pathogens. The molecular regulation of phagosome maturation is largely unknown. We show that integrin beta(1) plays critical roles in the phagocytosis of microbial pathogens and phagosome maturation. Macrophages lacking integrin beta(1) expression exhibit reduced phagocytosis of bacteria, including group B streptococcus and Staphylococcus aureus. Furthermore, phagosomes from macrophages lacking integrin beta(1) show lowered maturation rate, defective acquisition of lysosome membrane markers, and reduced F-actin accumulation in the periphagosomal region. Integrin beta(1)-deficient macrophages exhibit impaired bactericidal activity. We found that the expression of the Rho family GTPases Rac1, Rac2, and Cdc42 was reduced in integrin beta(1)-deficient macrophages. Ectopic expression of Rac1, but not Cdc42, in integrin beta(1)-deficient macrophages restored defective phagosome maturation and F-actin accumulation in the periphagosomal region. Importantly, macrophages lacking Rac1/2 also exhibit defective maturation of phagosomes derived from opsonized Escherichia coli or IgG beads. Taken together, these results suggest that integrin beta(1) regulates phagosome maturation in macrophages through Rac expression.
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- rac1 GTP-Binding Protein
- rac GTP-Binding Proteins
- Streptococcus agalactiae
- Staphylococcus aureus
- RAC2 GTP-Binding Protein
- Phagosomes
- Phagocytosis
- Neuropeptides
- Mice, Transgenic
- Mice, Knockout
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- rac1 GTP-Binding Protein
- rac GTP-Binding Proteins
- Streptococcus agalactiae
- Staphylococcus aureus
- RAC2 GTP-Binding Protein
- Phagosomes
- Phagocytosis
- Neuropeptides
- Mice, Transgenic
- Mice, Knockout