Quantum dots impair macrophagic morphology and the ability of phagocytosis by inhibiting the Rho-associated kinase signaling

Abstract

Quantum dots (QDs) are fluorescent semiconductor nanoparticles that have broad excitation spectra, narrow emission peaks, long fluorescence lifetimes, and the ability to easily conjugate with bio-molecules. Due to these distinct characteristics, QDs represent promising substances in biological imaging and labelling. However, the side and adverse effects of QDs are also widely studied. Herein, we recognize macrophages as the pivotal cells in ingesting QDs, and that the accumulation of QDs inside macrophages leads to significant morphological alterations and a remarkable reduction of their ability to erythrophagocytize in vitro. In a mouse model with chronic exposure to QDs, red blood cell (RBC) retention in spleens and severe splenomegaly were observed, presumably due to attenuated macrophagic erythrophagocytosis in vivo. Importantly, we demonstrated that QDs greatly inhibited the Rho-associated kinase (ROCK) activity, resulting in impaired fidelity of the actin cytoskeleton and actin-rich structure (such as surface protrusions), which was assumed to be the molecular basis underlying the blunted macrophagic morphology and reduced ability to phagocytize. The combined data provide insights into QDs' intracellular trafficking, localization and biological fate in macrophages, and the resultant impairment to cytoskeleton coupled with inhibition on the ROCK signalling would decrease the macrophagic ability to erythrophagocytize with diminished RBC recycling and splenic RBC retention in animals.

Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element

“…Cell experiments were similar to the standard instruction described in our recent publications (Liu et al, 2011;Qu et al, 2012).…”

Disordered hepcidin–ferroportin signaling promotes breast cancer growth

“…Solid tissues were snap-frozen in liquid nitrogen and homogenized in the abovementioned lysis buffer. Equal amounts of protein lysates (30-50 μg/sample) were subject to 8-12% SDS-PAGE and Western blot analysis as described previously [22]. Antibodies were anti-GAPDH (1:1000, Santa Cruz Biotechnology), ferritin light chain antibody (1:500, Abcam) and ferroportin antibody (1:500, Sigma-Aldrich).…”

Disordered signaling governing ferroportin transcription favors breast cancer growth

“…Total proteins were extracted with ice-cold RIPA lysis buffer (Solarbio, China) with protease inhibitor cocktail (Roche). Equal amounts of protein lysates were subjected to immunoblot according to the method described previously [26], using the following antibodies, GAPDH (1:1000, Santa Cruz Biotechnology), MZF-1 (1:200, Santa Cruz Biotechnology), Nrf2 (1:200, Santa Cruz Biotechnology), ferritin (1:500, Abcam) and FPN (1:500, Sigma-Aldrich).…”