Scavenger receptor-A functions in phagocytosis of E. coli by bone marrow dendritic cells.
Class-A scavenger receptors (SR-A) are cellular pattern recognition receptors that bind and traffic a variety of endogenous and microbial ligands. However, despite an emerging role for SR-A as a contributor to the innate immune system, little is known of the regulation or function of SR-A on dendritic cells (DCs). Here we show that SR-A expression is upregulated during murine DC differentiation and that SR-A expression levels correlate with the expression of the murine DC marker CD11c. Using bone marrow-derived DCs (BMDCs) from SR-A knockout (SR-A(-/-)) mice, we investigated the contribution of SR-A to BMDC particulate phagocytosis. Functional analyses demonstrated that SR-A is a critical phagocytic receptor for BMDC internalization of the gram-negative bacteria E. coli. SR-A(-/-) BMDCs were impaired in their ability to phagocytose bacteria, and this deficit varied with the bacteria:BMDC cell ratio. Microscopic and biochemical analyses revealed that SR-A is broadly distributed on the surface of BMDCs and is not physically associated with lipid rafts. However, cholesterol depletion demonstrated dependence of SR-A-mediated phagocytosis upon lipid rafts. These data demonstrate a functional contribution for SR-A in the BMDC phagocytic pathway.
Amiel
Eyal
E
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Nicholson-Dykstra
Susan
S
Walters
Julie Jo
JJ
Higgs
Henry
H
Berwin
Brent
B
D000818:Animals; D001854:Bone Marrow Cells / Q000382:microbiology / Q000502:physiology*; D018845:CD11 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000382:microbiology / Q000502:physiology*; D004926:Escherichia coli / Q000502:physiology; D006358:Hot Temperature; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D017434:Protein Structure, Tertiary; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D018845:CD11 Antigens; D051117:Scavenger Receptors, Class A