A Murine Scavenger Receptor MARCO Recognizes Polystyrene Nanoparticles

Abstract

Recent toxicological studies indicate that nanoparticles or ultrafine particles (< 100 nm) are more toxic than fine particles (< 2 microm) because of their greater surface area. It is well known that alveolar macrophages play an important role in the first defense against various environmental particles and microorganisms. This is accomplished by binding to a macrophage receptor with collagenous structure (MARCO), one of several scavenger-type receptors expressed on the cell surface of macrophages. MARCO has been shown to mediate the ingestion of unopsonized environmental particles such as TiO(2) and Fe(2)O(3) (1.3 microm in diameter). However, very little is known about the cellular uptake of nanoparticles. In the present study, we investigated whether MARCO mediates the uptake of nanoparticles by using fluorescent-tagged polystyrene particles (20 nm, 200 nm, and 1 microm in diameter). COS-7 cells were transfected with either MARCO cDNA or an empty vector, and the association of the particles with the cells were observed by fluorescence microscopy and atomic force microscopy. MARCO-transfected cells associated with all three sizes of particles in a time-dependent manner, while no obvious binding of particles occurred after 5 h to the empty vector-transfected cells. The uptake of particles by MARCO-transfected cells was partially inhibited by polyG. These results suggest that macrophages associate with nanoparticles (20 nm) at least in part through MARCO and that MARCO plays a role in clearing nanoparticles which can deposit in the alveolar region.

Ageing and the immune system: focus on macrophages

“…Opsonin-independent receptors include scavenger receptors which bind to a variety of substances, including modifi ed lipoproteins. Macrophage receptor with a collagenous structure (MARCO), a class A scavenger receptor, can bind gram-negative and gram-positive bacteria and has been suggested to be involved in the uptake of polystyrene particles [34]. Many opsonin-independent receptors bind to conserved microbial structures.…”

MARCO Regulates Early Inflammatory Responses against Influenza

“…These pattern recognition molecules mediate recognition and uptake of foreign material and modified host molecules (e.g., oxidized proteins and lipids) and exhibit a large array of ligand specificity. Lung macrophages use scavenger receptor A (SRA)-1 and macrophage receptor with collagenous structure (MARCO) to mediate uptake and clearance of lung pathogens, Streptococcus, unopsonized micro-and nanoparticulate matter, and ozonegenerated oxidized lipid intermediates (15)(16)(17)(18)(19). In all these studies, MARCO 2/2 mice showed increased morbidity or mortality because of decreased macrophage-mediated uptake and clearance, leading to exacerbated neutrophil response and enhanced lung pathology.…”

Experimental Therapeutics of Nrf2 as a Target for Prevention of Bacterial Exacerbations in COPD

“…To test the hypothesis that enhanced oxidative stress associated with Nrf2 deficiency impairs the clearance of respiratory infections, we identified a previously unknown role of Nrf2 in regulating expression of the scavenger receptor macrophage receptor with collagenous structure (MARCO). MARCO aids in the binding and uptake of bacteria, oxidized low-density lipoproteins, and environmental particles (42,43). MARCO is highly expressed in tissue (liver or lung) macrophages in response to bacterial infection, and genetic ablation of MARCO enhances bacterial colonization, inflammation, and diminished survival in a model of pneumococcal pneumonia (43).…”