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Divergent effects of methylxanthines and adenylate cyclase agonists on monocyte cytotoxicity and cyclic AMP levels
Author(s) -
HERLIN TROELS,
KRAGBALLE KNUD
Publication year - 1982
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1982.tb02235.x
Subject(s) - ibmx , antibody dependent cell mediated cytotoxicity , monocyte , theophylline , adenylate kinase , endocrinology , medicine , chemistry , phosphodiesterase , cyclase , cyclic adenosine monophosphate , cytotoxicity , forskolin , biochemistry , biology , receptor , stimulation , enzyme , in vitro
. Abstract. The effects of theophylline, isobutylmethyl‐xanthine (IBMX), prostaglandin El (PGE,), and iso‐proterenol on monocyte antibody‐dependent cytotoxi‐city (ADCC) were compared with their effects on monocyte cyclic adenosine 3′:5′‐monophosphate (CAMP) levels. Theophylline (2 mmol/l) halved ADCC and gave a 2‐fold increase in cAMP levels. At concen‐trations not elevating cAMP theophylline inhibited ADCC significantly. In comparison, incubation of monocytes with IBMX, PGEl and isoproterenol ADCC was only modestly inhibited while these agents gave larger increments (3‐to 8‐fold) in cAMP levels than theophylline did. Low concentrations of IBMX (50 pmol/l) elevated cAMP without affecting mono‐cyte ADCC whereas PGE, and isoproterenol inhibited ADCC dose‐dependently comparable to increases in CAMP. However, in doses giving similar inhibition of ADCC addition of PGEl resulted in larger cAMP increments than isoproterenol. The effects of IBMX, PGEl and isoproterenol was dependent on target cell to effector cell ratio and increased during preincuba‐tion with the agents. The inhibition of ADCC by the agents was accompanied by a depressed monocyte lysozyme release and depressed activation of hexose monophosphate shunt. However, only theophylline affected monocyte attachment to sensitized target cells. These results argue against the general inverse relationship between cAMP content and inhibition of monocyte ADCC and demonstrate that theophylline independent on increases in cAMP inhibits ADCC probably by abrogation of monocyte binding activity.