title: Cellular recognition and trafficking of amorphous silica nanoparticles by macrophage scavenger receptor A.
abstract: The cellular uptake of engineered nanoparticles (ENPs) is known to involve active transport mechanisms, yet the biological molecules involved are poorly understood. We demonstrate that the uptake of amorphous silica ENPs by macrophage cells, and the secretion of proinflammatory cytokines, is strongly inhibited by silencing expression of scavenger receptor A (SR-A). Conversely, ENP uptake is augmented by introducing SR-A expression into human cells that are normally non-phagocytic. Confocal microscopy analyses show that the majority of single or small clusters of silica ENPs co-localize with SR-A and are internalized through a pathway characteristic of clathrin-dependent endocytosis. In contrast, larger silica ENP agglomerates (>500 nm) are poorly co-localized with the receptor, suggesting that the physical agglomeration state of an ENP influences its cellular trafficking. As SR-A is expressed in macrophages throughout the reticulo-endothelial system, this pathway is likely an important determinant of the biological response to ENPs.
authors.affiliation: Chemical Physics & Analysis, Pacific NorthwestNational Laboratory, Richland, Washington, USA.
authors.forename: Galya A
authors.initials: GA
authors.lastname: Orr
authors.forename: William B
authors.initials: WB
authors.lastname: Chrisler
authors.forename: Kaylyn J
authors.initials: KJ
authors.lastname: Cassens
authors.forename: Ruimin
authors.initials: R
authors.lastname: Tan
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Tarasevich
authors.forename: Lye Meng
authors.initials: LM
authors.lastname: Markillie
authors.forename: Richard C
authors.initials: RC
authors.lastname: Zangar
authors.forename: Brian D
authors.initials: BD
authors.lastname: Thrall
mesh_terms: D000818:Animals; D002966:Clathrin; D004705:Endocytosis; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D002966:Clathrin; C495140:Msr1 protein, mouse; D051117:Scavenger Receptors, Class A; D012822:Silicon Dioxide