Activation signals in human lymphocytes. Incorporation of polyunsaturated fatty acids into plasma membrane phospholipids regulates IL-2 synthesis via sustained activation of protein kinase C.
Human PBL activated with anti-TCR/CD3 mAb express high affinity receptors for IL-2, synthesize IL-2, and subsequently proliferate. In contrast, lymphocytes activated by dioctanoylglycerol (DiC8) and ionomycin express high affinity receptors; however, no IL-2 synthesis is detectable. Anti-TCR/CD3 antibodies, as well as DiC8 cause translocation of protein kinase C (PKC) from the cytosol to the plasma membrane. In DiC8-stimulated cells translocation of PKC is detectable after 15 min, then it declines to control levels. In lymphocytes activated by antiTCR/CD3 mAb translocation of PKC is detectable after 15 min, then it declines to control levels, followed by a second, long lasting activation of the enzyme up to 4 h. Addition of polyunsaturated fatty acids to DiC8 + ionomycin-treated cells leads to IL-2 synthesis and proliferation. Incorporation of poly-unsaturated fatty acids into plasma membrane phospholipids results in long term activation of PKC. The results suggest that elevated incorporation of polyunsaturated fatty acids and thus continuous activation and translocation of PKC represents a necessary early signal for IL-2 synthesis and proliferation in human lymphocytes.
Szamel
M
M
Institute of Molecular Pharmacology, Medical School Hannove, FRG.
Rehermann
B
B
Krebs
B
B
Kurrle
R
R
Resch
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004075:Diglycerides / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis*; D015759:Ionomycin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology*; D009637:Masoprocol / Q000494:pharmacology; D008563:Membrane Lipids / Q000502:physiology*; D010743:Phospholipids / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013110:Sphingosine / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D004075:Diglycerides; D005231:Fatty Acids, Unsaturated; D007376:Interleukin-2; D007546:Isoquinolines; D008041:Linoleic Acids; D008563:Membrane Lipids; D010743:Phospholipids; D010879:Piperazines; D011948:Receptors, Antigen, T-Cell; D015759:Ionomycin; D009637:Masoprocol; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004247:DNA; D019787:Linoleic Acid; D011493:Protein Kinase C; D013110:Sphingosine; D007213:Indomethacin