RT Journal Article
T1 Amoxicillin haptenates intracellular proteins that can be transported in exosomes to target cells.
A1 Sanchez-Gomez, F J
A1 Gonzalez-Morena, J M
A1 Vida, Y
A1 Perez-Inestrosa, E
A1 Blanca, M
A1 Torres, M J
A1 Perez-Sala, D
K1 Amoxicillin
K1 Cellular protein targets
K1 Drug adducts
K1 Exosomes
K1 Haptenation
AB Allergic reactions to β-lactams are among 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. We have treated B lymphocytes with either AX or a biotinylated analog (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. 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. These results represent 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.
PB Wiley
YR 2017
FD 2017-02-17
LK http://hdl.handle.net/10668/10190
UL http://hdl.handle.net/10668/10190
LA en
NO Sánchez-Gómez FJ, González-Morena JM, Vida Y, Pérez-Inestrosa E, Blanca M, Torres MJ, et al. Amoxicillin haptenates intracellular proteins that can be transported in exosomes to target cells. Allergy. 2017 Mar;72(3):385-396
NO This work was supported by grants SAF2015-68590R/FEDER, SAF2012-36519 from MINECO, Spain, and RIR-AAF/RD12/0013/0008 from ISCIII to D.P.-S.; by grants CTQ2013-41339-P from MINECO, Spain, and RD12/0013/0003 from ISCIII to E. P-I.; and by grants PI12/02529 and PI15/01206 from MINECO grant cofunded by ERDF, Spain, RIRAAF/RD12/0013/0001 from ISCIII, CTS-06603 from Junta de Andalucía, grant cofunded by the ERDF, PI-0545-2010, PI-0551, and PI-0699-2011 from Junta de Andalucía to M.J.T and M.B.
DS RISalud
RD Apr 6, 2025