ANTIBIOTIC-INDUCED RELEASE OF SMALL EXTRACELLULAR VESICLES (EXOSOMES) WITH SURFACE-ASSOCIATED DNA

Recently, biological roles of extracellular vesicles (including exosomes, microvesicles and apoptotic bodies) have attracted substantial attention in various fields of biomedicine. Here the authors investigated the impact of sustained exposure of Jurkat cells to the fluoroquinolone antibiotic ciprofloxacin on the released extracellular vesicles. Ciprofloxacin is widely used in humans against bacterial infections as well as in cell cultures against Mycoplasma contamination. However, ciprofloxacin is an inducer of oxidative stress and mitochondrial dysfunction of mammalian cells. The authors found that ciprofloxacin induced the release of both DNA (mitochondrial and chromosomal sequences) and DNA-binding proteins on the surfaces of exosomes. Furthermore, a label-free optical biosensor analysis revealed DNA-dependent binding of exosomes to fibronectin. DNA release on the surface of exosomes was not affected any further by cellular activation or apoptosis induction.

Additionally, activation or apoptosis induction had an impact on the association of DNA with EVs of ciprofloxacin-exposed Jurkat cells. Results shows that apoptotic Jurkat cells secreted higher number of apoptotic bodies and microvesicles than either the controls or the activated cells. In contrast, a very high number of exosomes compared to apoptotic bodies and microvesicles was secreted by activated cells.

Proteomic analysis showed that apoptotic bodies and microvesicles released by apoptotic cells carried high number of unique proteins which were not shared with apoptotic bodies released by either control or activated cells. Apoptotic cell-derived apoptotic bodies contained peroxiredoxin-6, septin 7, septin 9, annexin A7, poly (ADP-ribose) polymerase 1. Proteins unique to apoptotic cell-derived microvesicles included destrin, integrin beta 2, vesicle associated membrane protein 5, tetraspanin-14 and heat shock protein 105 kDa. In a comparison of exosomes released by control to activated and apoptotic cells, exosomes secreted upon cell activation contained the highest number of unique proteins, for example ATP synthase subunit beta, copine-3, replication protein A, cell division control protein, chloride intracellular channel protein 1, tyrosine-protein kinase ITK/TSK.

Reference: Andrea Németh et al . Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA. Scientific Reports, Volume 7, (2017)

Than Thi Trang Uyen, PhD