| Autor: |
Alberto Molano, Zhaofeng Huang, Melissa G Marko, Angelo Azzi, Dayong Wu, Elaine Wang, Samuel L Kelly, Alfred H Merrill, Stephen C Bunnell, Simin Nikbin Meydani |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 7, Iss 10, p e47650 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0047650 |
| Popis: |
To determine whether changes in sphingolipid composition are associated with age-related immune dysfunction, we analyzed the core sphingolipidome (i.e., all of the metabolites through the first headgroup additions) of young and aged CD4(+) T cells. Since sphingolipids influence the biophysical properties of membranes, we evaluated the compositions of immune synapse (IS) and non-IS fractions prepared by magnetic immuno-isolation. Broadly, increased amounts of sphingomyelins, dihydrosphingomyelins and ceramides were found in aged CD4(+) T cells. After normalizing for total sphingolipid content, a statistically significant decrease in the molar fraction of glucosylceramides was evident in both the non-IS and IS fractions of aged T cells. This change was balanced by less dramatic increases in the molar fractions of sphingomyelins and dihydrosphingomyelins in aged CD4(+) T cells. In vitro, the direct or enzymatic enhancement of ceramide levels decreased CD4(+) T cell proliferation without regard for the age of the responding T cells. In contrast, the in vitro inhibition of glucosylceramidase preferentially increased the proliferation of aged CD4(+) T cells. These results suggest that reductions in glucosylceramide abundance contribute to age-related impairments in CD4(+) T cell function. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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