PMID- 34378992 OWN - NLM STAT- MEDLINE DCOM- 20210921 LR - 20220902 IS - 1522-1563 (Electronic) IS - 0363-6143 (Print) IS - 0363-6143 (Linking) VI - 321 IP - 3 DP - 2021 Sep 1 TI - Class A scavenger receptor-1/2 facilitates the uptake of bovine milk exosomes in murine bone marrow-derived macrophages and C57BL/6J mice. PG - C607-C614 LID - 10.1152/ajpcell.00222.2021 [doi] AB - 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. FAU - Khanam, Afsana AU - Khanam A AUID- ORCID: 0000-0001-9813-5138 AD - Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska. FAU - Yu, Jiujiu AU - Yu J AD - Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska. FAU - Zempleni, Janos AU - Zempleni J AUID- ORCID: 0000-0001-5492-4661 AD - Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska. LA - eng SI - figshare/10.6084/m9.figshare.14763363.v5 GR - P20 GM104320/GM/NIGMS NIH HHS/United States GR - P20GM104320/HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20210811 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (Fluorescent Dyes) RN - 0 (Msr1 protein, mouse) RN - 0 (Protein Isoforms) RN - 0 (Scavenger Receptors, Class A) RN - 0813BZ6866 (Clodronic Acid) RN - 22144-77-0 (Cytochalasin D) SB - IM MH - Animals MH - Cattle MH - Clodronic Acid/pharmacology MH - Cytochalasin D/pharmacology MH - Endocytosis/drug effects MH - Exosomes/chemistry/*metabolism MH - Female MH - Fluorescent Dyes/chemistry MH - Gene Expression MH - Liver/drug effects/metabolism MH - Lung/drug effects/metabolism MH - Macrophages/cytology/drug effects/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Milk/*chemistry MH - Phagocytosis/drug effects MH - Protein Isoforms/deficiency/genetics MH - Scavenger Receptors, Class A/deficiency/*genetics MH - Spleen/drug effects/metabolism MH - Staining and Labeling/methods PMC - PMC8461812 OTO - NOTNLM OT - bone marrow-derived macrophages OT - bovine OT - class A scavenger receptors OT - milk exosomes OT - phagocytosis COIS- J.Z. serves as a consultant for PureTech Health, Inc. None of the other authors has any conflicts of interest, financial or otherwise, to disclose. EDAT- 2021/08/12 06:00 MHDA- 2021/09/22 06:00 PMCR- 2022/09/01 CRDT- 2021/08/11 12:12 PHST- 2021/08/12 06:00 [pubmed] PHST- 2021/09/22 06:00 [medline] PHST- 2021/08/11 12:12 [entrez] PHST- 2022/09/01 00:00 [pmc-release] AID - C-00222-2021 [pii] AID - 10.1152/ajpcell.00222.2021 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2021 Sep 1;321(3):C607-C614. doi: 10.1152/ajpcell.00222.2021. Epub 2021 Aug 11.