Cellular cholesterol enrichment impairs T cell activation and chemotaxis.
Mech Ageing Dev
; 125(9): 641-50, 2004 Sep.
Article
em En
| MEDLINE
| ID: mdl-15491683
ABSTRACT
Human aging is associated with an increase in immune cell cholesterol levels, independent of circulating cholesterol levels. The effects of such an increase in membrane cholesterol on lipid raft-associated immune cell function have not been investigated. We sought to examine the effects of in vitro cholesterol loading on two known lipid raft-associated pathways of T cells, namely T cell activation and chemokine stimulation. Using beta-cyclodextrin (BCD) as a vehicle, we were able to rapidly load cholesterol onto human T cell lines and primary peripheral blood T cells without inducing significant cell toxicity. Loading of cholesterol to four-fold that of normal levels induced significant inhibition of intracellular calcium mobilization by both alphaCD3 and SDF-1alpha. Cholesterol-loaded peripheral T cells were completely unresponsive to alphaCD3/alphaCD28 stimulation, demonstrating no increase in IL-2, GM1 expression or cell size. T cell polarization of lipid rafts to alphaCD3/alphaCD28 beads was also impaired. In addition, cholesterol loading potently inhibited SDF-1alpha-induced chemotaxis. We propose that excess membrane cholesterol could potentially disrupt raft-related cell functions downstream of receptor triggering and that the loss of cholesterol regulation of aging immune cells could contribute to immune cell senescence.
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Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Linfócitos T
/
Colesterol
Limite:
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article