2024-03-28T15:21:07Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1519332020-11-12T14:28:28Zcom_10261_86com_10261_1col_10261_339
DIGITAL.CSIC
author
Sánchez-Gómez, Francisco J.
author
González-Morena, Juan M.
author
Vida, Yolanda
author
Pérez-Inestrosa, Ezequiel
author
Blanca, Miguel
author
Torres, María J.
author
Pérez-Sala, Dolores
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
funder
Junta de Andalucía
2017-06-23T12:37:47Z
2017-06-23T12:37:47Z
2017-03
Allergy 72(3) 385-396 (2017)
0105-4538
http://hdl.handle.net/10261/151933
10.1111/all.12958
1398-9995
http://dx.doi.org/10.13039/501100003329http://dx.doi.org/10.13039/501100004587http://dx.doi.org/10.13039/501100011011
Background :Allergic reactions to β-lactams are amongst the most frequent causes of drug allergy and constitute an important clinical problem. Drug covalent binding to endogenous proteins (haptenation) is thought to be required for activation of the immune system. Nevertheless, neither the nature nor the role of the drug protein targets involved in this process is fully understood. Here we aim to identify novel intracellular targets for haptenation by amoxicillin (AX) and their cellular fate.
Methods: We have treated B-lymphocytes with either AX or a biotinylated analogue (AX-B). The identification of protein targets for haptenation by AX has been approached by mass spectrometry and immunoaffinity techniques. In addition, intercellular communication mediated by the delivery of vesicles loaded with AX-B-protein adducts has been explored by microscopy techniques.
Results: We have observed a complex pattern of AX-haptenated proteins. Several novel targets for haptenation by AX in B-lymphocytes have been identified. AX-haptenated proteins were detected in cell lysates and extracellularly, either as soluble proteins or in lymphocyte-derived extracellular vesicles. Interestingly, exosomes from AX-B-treated cells showed a positive biotin signal in electron microscopy. Moreover, they were internalized by endothelial cells, thus supporting their involvement in intercellular transfer of haptenated proteins.
Conclusions: These results constitute the first identification of AX-mediated haptenation of intracellular proteins. Moreover, they show that exosomes can constitute a novel vehicle for haptenated proteins, and raise the hypothesis that they could provide antigens for activation of the immune system during the allergic response.
eng
openAccess
Amoxicillin
Cellular protein targets
Drug adducts
Exosomes
Haptenation
Amoxicillin haptenates intracellular proteins that can be transported in exosomes to target cells
artículo
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URL
https://digital.csic.es/bitstream/10261/151933/1/Sanchez-Gomez%20%202017.pdf
File
MD5
be9255457d899720d4f0d5d11e09a591
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application/pdf
Sanchez-Gomez 2017.pdf