Incorporation, distribution, and turnover of arachidonic acid within membrane phospholipids of B220+ T cells from autoimmune-prone MRL-lpr/lpr mice.
The metabolism of AA-containing phosphoglycerides within T cell membranes leads to the generation of second messengers that appear to play a crucial role in transmembrane signal transduction. To test the hypothesis that aberrations in the movement of arachidonoyl-phospholipids are associated with and may potentially contribute to abnormal T cell function, the incorporation, distribution, and turnover of AA within the membrane glycerolipids of cells that are known to exhibit immunoregulatory disturbances was examined. Thy-1+, Ly-1+, L3T4-, Lyt-2-, B220+ T cells from autoimmune MRL-lpr/lpr mice were used as the cellular model. In contrast to control lymph node T cells, which preferentially incorporate labeled AA into phosphatidylcholine (PC), B220+ T cells displayed a predilection for distributing [3H]arachidonate into phosphatidylinositol (PI). The arachidonoyl-phospholipid pools were normal in B220+ T cells. The constitutive turnover of [3H]arachidonoyl-PI was significantly enhanced and that of [3H]arachidonate-PC substantially reduced in B220+ T cell compared with control cells. Using membrane homogenates B220+ T cells demonstrated a functional increase in the levels of lyso-PI. Intact B220+ T cells prelabeled with [3H]myoinositol and cultured in the absence of stimulation with exogenous antigens or mitogens, exhibited increased production of lyso-PI. The data indicate that the preferential formation of [3H]arachidonoyl-PI in B220+ T cells is the result of greatly increased, constitutive PI turnover that appears to be due to a membrane phospholipase A2 activity. It remains possible that disturbances in the movement of arachidonate within phospholipids of B220+ T cells play a role in the expression of aberrant immunological activity.
Tomita-Yamaguchi
M
M
Department of Medicine, University of Colorado Health Sciences Center, Denver.
Babich
J F
JF
Baker
R C
RC
Santoro
T J
TJ
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D010740:Phospholipases / Q000032:analysis; D010743:Phospholipids / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D001095:Arachidonic Acids; D008246:Lysophospholipids; D008563:Membrane Lipids; D010743:Phospholipids; C025449:lysophosphatidylinositol; D016718:Arachidonic Acid; D010740:Phospholipases