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J Am Soc Nephrol. 2014 Sep;25(9):2017-27. doi: 10.1681/ASN.2013101066. Epub 2014 Apr 3.

Human urinary exosomes as innate immune effectors.

Author information

1
Department of Medicine, Cambridge Centre for Proteome Research and Cambridge Systems Biology Centre, Department of Biochemistry.
2
Cambridge Centre for Proteome Research and Cambridge Systems Biology Centre, Department of Biochemistry.
3
Department of Medical Genetics, and.
4
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
5
Department of Medicine.
6
Multi-Imaging Centre, Department of Anatomy, University of Cambridge, Cambridge, United Kingdom; and.
7
Cambridge Centre for Proteome Research and Cambridge Systems Biology Centre, Department of Biochemistry, ksl23@cam.ac.uk fek1000@cam.ac.uk.
8
Department of Medical Genetics, and ksl23@cam.ac.uk fek1000@cam.ac.uk.

Abstract

Exosomes are small extracellular vesicles, approximately 50 nm in diameter, derived from the endocytic pathway and released by a variety of cell types. Recent data indicate a spectrum of exosomal functions, including RNA transfer, antigen presentation, modulation of apoptosis, and shedding of obsolete protein. Exosomes derived from all nephron segments are also present in human urine, where their function is unknown. Although one report suggested in vitro uptake of exosomes by renal cortical collecting duct cells, most studies of human urinary exosomes have focused on biomarker discovery rather than exosome function. Here, we report results from in-depth proteomic analyses and EM showing that normal human urinary exosomes are significantly enriched for innate immune proteins that include antimicrobial proteins and peptides and bacterial and viral receptors. Urinary exosomes, but not the prevalent soluble urinary protein uromodulin (Tamm-Horsfall protein), potently inhibited growth of pathogenic and commensal Escherichia coli and induced bacterial lysis. Bacterial killing depended on exosome structural integrity and occurred optimally at the acidic pH typical of urine from omnivorous humans. Thus, exosomes are innate immune effectors that contribute to host defense within the urinary tract.

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PMID:
24700864
PMCID:
PMC4147985
DOI:
10.1681/ASN.2013101066
[Indexed for MEDLINE]
Free PMC Article
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