The Presence of Sulfo-Cerebrosides Upregulates Liposome Uptake by Human Astrocytes

Autor: John Mario González, Elizabeth Suesca, Chad Leidy, Jose L. Alejo Amaya, Natalia I. Bolaños
Rok vydání: 2011
Předmět:
Zdroj: Biophysical Journal. 100:410a
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2010.12.2430
Popis: Astrocytes are the most abundant cells of the central nervous system (CNS). In the CNS, astrocytes form part of the blood brain barrier, supply neurons and oligodendrocytes with substrates for energy metabolism, control homeostasis, regulate neurotransmitter release and modulate the immune response. Evidence indicates that astrocytes also play a key role in the pathogenesis of inflammatory CNS diseases. Particularly these cells are implicated in autoimmune and neurodegenerative diseases, such as multiple sclerosis and neuromyelitis optica, which are characterised by demyelinization. During demyelinization the glial cells could be exposed to lipid aggregates. For this reason. it is important to evaluate the effect of lipid aggregates in the functionality of astrocytes. As a first approximation, we evaluated the effects of myelin lipids on liposome uptake, cell viability and pro-inflamatory response in astrocytes. Experiments were carried out using a human astrocyte cell line, which was cultured with small unilamellar vesicles (SUVs) labeled with NBD-PE. By varying SUV composition (cholesterol, phospholipids, sphingomyelin, cerebrosides, ceramides and sulfo-cerebroside), myelin composition is mimicked, and its effects are evaluated. Vesicle uptake kinetics are monitored through fluorescence spectroscopy and corroborated through flow cytometry, whereas cell viability and proliferation, MHC molecules expression, and pro-inflammatory chemokine secretion are evaluated by flow cytometry. Results show significant uptakes for all compositions within 30 minutes, reaching saturation levels around 1 hour after exposure. Interestingly uptake was upregulated for vesicles containing sulfo-cerebrosides. Additionally, no pro-inflammatory response was observed under tested conditions and cell viability was not compromised. These results indicate that astrocytes can modulate lipid uptake based on lipid composition, and that this uptake mechanism does not induce a pro-inflamatory response in the cell population. These results point to a potential lipid homeostasis mechanism triggered by myelin lipids.
Databáze: OpenAIRE