Scavenger receptor MARCO contributes to cellular internalization of exosomes by dynamin-dependent endocytosis and macropinocytosis

Abstract

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor class-A protein that is expressed on the cell surface of macrophages. MARCO mediates binding and ingestion of unopsonized environmental particles, including nano-sized materials. Exosomes are cell-derived, nano-sized vesicles (40–150 nm) that can contain lipids, RNA, DNA, and various proteins. Exosomes play an essential role in cell-to-cell communication via body fluids. However, mechanisms for the recognition and internalization of exosomes by recipient cells remain poorly characterized. In this study, cellular association of serum-derived fluorescent exosomes and 20-nm fluorescent nanoparticles (positive control) was compared between MARCO-expressing (CHO-MARCO) and control (CHO-CT) CHO-K1 cells to examine whether MARCO expression by recipient cells mediates the cellular uptake of exosomes and environmental nanoparticles. Fluorescence microscopic studies and quantitative analyses revealed that the cellular associations of both exosomes and 20-nm nanoparticles were greater in CHO-MARCO cells than in CHO-CT cells. Exosomes and nanoparticles colocalized with green fluorescent protein (GFP)-MARCO in cells transfected with GFP-MARCO-encoding constructs . Furthermore, inhibitory studies showed that actin reorganization and dynamin are involved in the MARCO-mediated cellular internalization of exosomes. These results indicated that MARCO plays a role in the uptake of exosomes.

SARS-CoV-2 activates lung epithelial cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients

“…We also noticed that macrophages of severe COVID-19 patients expressed less MARCO. MARCO is expressed on alveolar macrophages and thought to promote protective innate immunity against infection [30] . Thus the immune system of severe COVID-19 patients failed to clean up SARS-CoV-2.…”

MARCO+ Macrophage Dynamics in Regenerating Liver after 70% Liver Resection in Mice

“…In summary, enhanced synthesis of the macrophage protein MARCO has been observed in murine liver macrophages after 70% resection. The increased expression of MARCO by macrophages can be regarded as a sign of their activation, due to the established functional association of this protein with endocytosis [ 14 , 15 ]. The obtained results complement the existing data on the LPS-induced increase in expression of MARCO in bone marrow-derived macrophages [ 14 , 57 ].…”

“…MARCO (abbreviated from macrophage receptor with collagenous structure), a scavenger receptor class A protein expressed on macrophages [ 14 , 15 ], has been featured as a liver mature macrophage-specific marker [ 16 , 17 ]. In this study, we estimate the dynamics of MARCO + macrophages in the liver after 70% hepatectomy in mice.…”

Exosomes as mediators of intercellular crosstalk in metabolism

“…This can include integrin-tetraspanin complexes (Hazawa et al, 2014;Jankovi cová et al, 2020), and/or binding of the exosomal ephrin receptor (Eph) to membranal ephrin expressed on recipient cells (Irie et al, 2009;Gong et al, 2016;Sato et al, 2019). Another example is the macrophage receptor with collagenous structure (MARCO), which can mediate exosome internalization by macro-phages (Kanno et al, 2020). In addition, exosome membrane proteins also modulate circulating kinetics.…”