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Integrin β₁ Regulates Phagosome Maturation in Macrophages through Rac Expression¹

Qing-Qing Wang^*, Hong Li^*, Tim Oliver, Michael Glogauer, Jian Guo^* and You-Wen He^2,*

Departments of ^* Immunology and Cell Biology, Duke University Medical Center, Durham, NC 27710; and Canadian Institute of Health Research, Group in Matrix Dynamics, Faculty of Dentistry, University of Toronto, Ontario, Canada

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 β₁ plays critical roles in the phagocytosis of microbial pathogens and phagosome maturation. Macrophages lacking integrin β₁ expression exhibit reduced phagocytosis of bacteria, including group B streptococcus and Staphylococcus aureus. Furthermore, phagosomes from macrophages lacking integrin β₁ show lowered maturation rate, defective acquisition of lysosome membrane markers, and reduced F-actin accumulation in the periphagosomal region. Integrin β₁-deficient macrophages exhibit impaired bactericidal activity. We found that the expression of the Rho family GTPases Rac1, Rac2, and Cdc42 was reduced in integrin β₁-deficient macrophages. Ectopic expression of Rac1, but not Cdc42, in integrin β₁-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 β₁ regulates phagosome maturation in macrophages through Rac expression.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by National Institutes of Health Grants AI054685 and AI061364 to Y.-W.H.

² Address correspondence and reprint requests to Dr. You-Wen He, Box 3010, Department of Immunology, Duke University Medical Center, Durham, NC 27710. E-mail address: he000004{at}mc.duke.edu

³ Abbreviations used in this paper: GBS, group B streptococcus; AF, Alexa Fluor; BMM, bone marrow-derived macrophage; DC, dendritic cell; FRET, fluorescence resonance energy transfer; hCD2, human CD2; LAMP, lysosomal-associated membrane protein; MFI, mean fluorescence intensity; WT, wild type.

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