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Class A scavenger receptor-1/2 facilitates the uptake of bovine milk exosomes in murine bone marrow-derived macrophages and C57BL/6J mice

Authors :
Afsana Khanam
Janos Zempleni
Jiujiu Yu
Source :
Am J Physiol Cell Physiol
Publication Year :
2021
Publisher :
American Physiological Society, 2021.

Abstract

Bovine milk exosomes (BMEs) are being explored in drug delivery despite their rapid elimination by macrophages. We aimed at identifying the BME transporter in murine bone marrow-derived macrophages (BMDMs). Fluorophore-labeled BMEs were used in transport studies in BMDMs from C57BL/6J and class A scavenger receptor type 1/2 (CASR-1/2) knockout mice and tissue accumulation in macrophage-depleted C57BL/6J mice. Parametric and nonparametric statistics tests for pairwise and multiple comparisons were used. Chemical inhibitors of phagocytosis by cytochalasin D led to a 69 ± 18% decrease in BME uptake compared with controls ( P < 0.05), whereas inhibitors of endocytic pathways other than phagocytosis had a modest effect on uptake ( P > 0.05). Inhibitors of class A scavenger receptors (CASRs) including CASR-1/2 caused a 70% decrease in BME uptake ( P < 0.05). The uptake of BMEs by BMDMs from CASR-1/2 knockout mice was smaller by 58 ± 23% compared with wild-type controls ( P < 0.05). Macrophage depletion by clodronate caused a more than 44% decrease in BME uptake in the spleen and lungs ( P < 0.05), whereas the decrease observed in liver was not statistically significant. In conclusion, CASR-1/2 facilitates the uptake of BMEs in BMDMs and C57BL/6J mice.

Details

ISSN :
15221563 and 03636143
Volume :
321
Database :
OpenAIRE
Journal :
American Journal of Physiology-Cell Physiology
Accession number :
edsair.doi.dedup.....4135755ef26ca0b6b5c3344c94596625
Full Text :
https://doi.org/10.1152/ajpcell.00222.2021