The Immunosuppressive Activities of Different Cyclosporins are Correlated to Inhibition of the Early Membrane Phospholipid Metabolism in Activated Lymphocytes

Recently, it could be shown that Cyclosporin A (CsA) inhibited the activation of T and B lymphocytes by interfering with an early step of the activation, namely the stimulation of the plasma membrane-bound lysophosphatide acyltransferase. In this report, we compared three CsA-derivatives, Dihydro-Cy...

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Bibliographic Details
Published in:Immunobiology (1979) 1987-09, Vol.175 (3), p.159-171
Main Authors: Kroggel, Roswitha, Goppelt-Strübe, Margarete, Martin, M., Resch, K.
Format: Article
Language:English
Subjects:
1-Acylglycerophosphocholine O-Acyltransferase - metabolism
Animals
Applied sciences
Cell Membrane - drug effects
Cell Membrane - metabolism
Cyclosporins - pharmacology
Exact sciences and technology
In Vitro Techniques
Lymphocyte Activation - drug effects
Lymphocytes - drug effects
Lymphocytes - metabolism
Membrane Lipids - metabolism
Other techniques and industries
Phospholipids - metabolism
Rabbits
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Summary:Recently, it could be shown that Cyclosporin A (CsA) inhibited the activation of T and B lymphocytes by interfering with an early step of the activation, namely the stimulation of the plasma membrane-bound lysophosphatide acyltransferase. In this report, we compared three CsA-derivatives, Dihydro-Cyclosporin C (Dihydro-CsC), «C 9-O-Acetyl»-CsA (CsA AC), Cyclosporin H (CsH), regarding the inhibition of proliferation and the interference with the activation of the phospholipid metabolism. At concentrations below 1 μ/ml, CsA AC and CsH had no effect on any parameter measured. Dihydro-CsC, however, closely resembled CsA: it inhibited the induction of DNA- and RNA-synthesis in T and B lymphocytes from mesenteric lymph nodes of rabbits. Similar to CsA, Dihydro-CsC also interfered with the enhanced incorporation of arachidonic acid into plasma membrane phospholipids by inhibiting the activation of the lysophosphatide acyltransferase. The close correlation between inhibition of proliferation and interferences with the phospholipid metabolism of the plasma membrane suggested that Dihydro-CsC as well as CsA interfered with an early step of lymphocyte activation at the level of the plasma membrane.
ISSN:0171-2985
1878-3279
DOI:10.1016/S0171-2985(87)80025-6