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PXD010760

PXD010760 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleExosomal transport of hepatocyte-derived drug-modified proteins to the immune system
DescriptionIdiosyncratic drug-induced liver injury (DILI) is a rare, often difficult to predict adverse reaction with complex pathomechanisms. However, it is now evident that certain forms of DILI are immune-mediated and may involve the activation of drug-specific T-cells. Exosomes are cell-derived vesicles that carry RNA, lipids and protein cargo from their cell of origin to distant cells, and may play a role in immune activation. Herein, primary human hepatocytes were treated with drugs associated with a high incidence of DILI (flucloxacillin, amoxicillin, isoniazid and nitroso-sulfamethoxazole) to characterize the proteins packaged within exosomes that are subsequently transported to dendritic cells for processing. Exosomes measured between 50-100 nm and expressed CD63. LC-MS/MS identified an average of 1200 proteins across all exosome samples. Analysis of gene ontologies revealed that exosomes mirrored whole human liver tissue in terms of the families of proteins present, regardless of drug treatment. However, exosomes from nitroso-sulfamethoxazole-treated hepatocytes selectively packaged a specific subset of proteins. LC-MS also revealed the presence of hepatocyte-derived exosomal proteins covalently modified with amoxicillin, flucloxacillin and nitroso-sulfamethoxazole. Uptake of exosomes by monocyte-derived dendritic cells occurred mainly via phagocytosis, and was inhibited by latrunculin A. This study reveals that exosomes have the potential to transmit drug-specific hepatocyte-derived signals to the immune system and provides a pathway for the induction of drug hapten-specific T-cell responses.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:47:38.896.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRosalind Jenkins
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; acetylated residue; deamidated residue
InstrumentSCIEX instrument model
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-08-13 07:38:50ID requested
12019-05-14 07:16:12announced
22024-10-22 04:47:41announced2024-10-22: Updated project metadata.
Publication List
Ogese MO, Jenkins RE, Adair K, Tailor A, Meng X, Faulkner L, Enyindah BO, Schofield A, Diaz-Nieto R, Ressel L, Eagle GL, Kitteringham NR, Goldring CE, Park BK, Naisbitt DJ, Betts C, Exosomal Transport of Hepatocyte-Derived Drug-Modified Proteins to the Immune System. Hepatology, 70(5):1732-1749(2019) [pubmed]
10.1002/hep.30701;
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: exosomes,Hepatocytes, immune response, drug-induced liver injury
Contact List
Rosalind Jenkins
contact affiliationMRC Centre for Drug Safety Science, Dept Molecular and Clinical Pharmacology, University of Liverpool
contact emailR.Jenkins@liv.ac.uk
lab head
Rosalind Jenkins
contact affiliationUniversity of Liverpool
contact emailR.Jenkins@liv.ac.uk
dataset submitter
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Dataset FTP location
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PRIDE project URI
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