Cellular recognition and trafficking of amorphous silica nanoparticles by macrophage scavenger receptor A.
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.
Orr
Galya A
GA
Chemical Physics & Analysis, Pacific NorthwestNational Laboratory, Richland, Washington, USA.
Chrisler
William B
WB
Cassens
Kaylyn J
KJ
Tan
Ruimin
R
Tarasevich
Barbara J
BJ
Markillie
Lye Meng
LM
Zangar
Richard C
RC
Thrall
Brian D
BD
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*
D002966:Clathrin; C495140:Msr1 protein, mouse; D051117:Scavenger Receptors, Class A; D012822:Silicon Dioxide