Molecular basis for the immunosuppressive action of stearic acid on T cells.
Studies were performed to determine the mechanism by which stearic acid (18:0) selectively inhibits T-dependent immune responses in vitro. Incubation of mitogen-activated B and T cells with 18:0 resulted in dissimilar patterns of incorporation of the saturated fatty acid into their membranes. High-performance liquid chromatography (HPLC) analyses of T cells showed an accumulation of disaturated [corrected] 18:0-containing phosphatidylcholine (PC) that replaced normal cellular PC. Less significant quantities of the same PC species were seen to accumulate in B-cell membranes; rather, they increased their proportion of oleic acid (18:1)-containing PC. The different lipid compositions of the lymphocyte cell membranes after exposure to 18:0 were correlated with their plasma membrane potentials. In T cells, the accumulation of disaturated [corrected], 18:0-containing PC coincided with a rapid (within 8 hr) collapse of membrane integrity, as determined by flow cytometry. The collapse of membrane integrity was found to be time and dose dependent. No such depolarization was observed in B cells which, by virtue of their desaturating ability, were able to avoid incorporating large amounts of disaturated [corrected] 18:0-containing phospholipids into their membranes. It is proposed that a lack of stearoyl-CoA desaturase in T cells precludes them from desaturating exogenously derived 18:0, thus leading to increased proportions of 18:0-containing disaturated [corrected] PC in their cell membranes. The increased abundance of this PC species may enhance membrane rigidity to an extent that plasma membrane integrity is significantly impaired, leading to a loss of membrane potential and ultimately cell function and viability.
Tebbey
P W
PW
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville 27858-4354.
Buttke
T M
TM
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010713:Phosphatidylcholines / Q000378:metabolism*; D013229:Stearic Acids / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D007166:Immunosuppressive Agents; D010713:Phosphatidylcholines; D013229:Stearic Acids