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MODULATION OF HUMAN LEUCOCYTE MIGRATION INHIBITORY FACTOR (LIF) BY 3', 5'‐CYCLIC AMP, 3', 5'‐CYCLIC GMP AND AGENTS KNOWN TO INFLUENCE INTRACELLULAR CYCLIC NUCLEOTIDE METABOLISM
Author(s) -
Bendtzen K.,
Palit J.
Publication year - 1977
Publication title -
acta pathologica microbiologica scandinavica section c immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0304-1328
DOI - 10.1111/j.1699-0463.1977.tb03649.x
Subject(s) - intracellular , phosphodiesterase , adenosine , papaverine , medicine , endocrinology , inhibitory postsynaptic potential , chemistry , cyclic nucleotide , propranolol , bucladesine , in vitro , adrenergic , nucleotide , pharmacology , enzyme , biology , biochemistry , receptor , gene
A study was made of the effects of 3', 5'‐cycylic AMP (3', 5' cAMP), 3', 5'‐cyclic GMP (3', 5' cGMP) and their dibutyryl derivatives, and the effects of various both cyclic and non‐cyclic nucleotides and of nucleosides on the in vitro migration of human peripheral blood leucocytes under agarose and on the activity of leucocyte migration inhibitory factor (LIF). Leucocyte migration was not significantly influenced by any of the above‐mentioned drugs. However, LIF activity was significantly depressed by 3', 5' cAMP and dibutyryl 3', 5' cAMP, whereas cells challenged with 10 ‐4 M of the other drugs, including 2', 3' cAMP, 3'‐AMP, 5'‐AMP and adenosine, showed unreduced migration inhibition under standard test conditions. A possible role of 3', 5' cAMP in the mechanism of LIF action was supported further by experiments with various drugs known to influence intracellular 3', 5' cAMP metabolism. Treatment of leucocytes with the 3', 5' cAMP generating, beta‐adrenergic agent isoproterenol (10 ‐4 M) caused a rapid, transient reduction of LIF activity as compared to LIF‐treated controls. The alfa‐adrenergic agent norepinephrine (10 ‐4 M) was ineffective. Treatment of leucocytes with the phosphodiesterase inhibitors papaverine (10 ‐4 M) and dipyridamole (2×10 ‐5 ) enhanced their motility and enabled them to escape migration inhibition as compared to LIF‐treated controls. 3', 5' cGMP may also participate in the expression of LIF activity, since cells treated with 3', 5' cGMP partially escaped migration inhibition during the first 3 hours of migration.