Abstract：
:The relationship between the phospholipase-stimulating and immunosuppressive properties of cyclosporin A (CsA) has been investigated in vitro. At concentrations of 0.025 microM and upwards, CsA caused dose-related inhibition of both mitogen- and alloantigen-stimulated uptake of tritiated thymidine by human mononuclear leukocytes (MNL), which was associated with a time- and dose-related enhancement of the generation of lysophosphatidylcholine (LPC), arachidonic acid, and prostaglandin E2 from mitogen-stimulated cells. Arachidonate alone, at concentrations of up to 20 microM, did not affect lymphocyte activation, whereas cyclooxygenase and 5'-lipoxygenase inhibitors failed to protect the cells against the antiproliferative effects of CsA. However, LPC caused dose-related inhibition of MNL proliferation. Moreover, coincubation of MNL with alpha-tocopherol, a lysophospholipid-complexing agent, or with lysophospholipase protected the cells against CsA, as well as against LPC. The Na+,K(+)-ATPase activity of mitogen-activated lymphocytes was also inhibited by CsA, whereas inclusion of alpha-tocopherol or lysophospholipase protected this enzyme. Excessive production of lysophospholipids and consequent inhibition of Na+,K(+)-ATPase during CsA treatment of mitogen- or antigen-activated lymphocytes is a possible biochemical mechanism of the immunosuppressive activity of this agent.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Anderson R,Smit MJ,Van Rensburg CEsubject
Has Abstractpub_date
1993-09-01 00:00:00pages
605-14issue
3eissn
0026-895Xissn
1521-0111journal_volume
44pub_type
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