The mechanism of antibody-dependent cellular cytotoxicity stimulation by somatostatin in rat peritoneal macrophages.
Somatostatin (SS) in 10(-9)-10(-7) M concentrations stimulated the lysis and inhibited the incorporation of IgG2a-coated 51Cr-labeled sheep red blood cell (SRBC) by rat peritoneal macrophages (PM). The intracellular killing capacity of PM remained unchanged. The enhancement of Fc receptor (R) activity and generation of active oxygen species were found to be responsible for the antibody-dependent cellular cytotoxicity (ADCC)-stimulating effect of SS. It was demonstrated that the stimulation of ADCC was abolished by the calmodulin inhibitor trifluoperazine (TFP), whereas it proved to be independent of the Ca2+ uptake. In addition, SS in the ADCC-stimulating concentrations diminished the intracellular cAMP generation and progressively increased the cGMP level. In higher (10(-6)-10(-7) M) concentrations, SS had a controversial effect on PM: it inhibited ADCC through the activation of both the adenylate cyclase and Ca2+ influx.
Fóris
G
G
Gyimesi
E
E
Komáromi
I
I
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008297:Male; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D011961:Receptors, Fc / Q000187:drug effects; D013004:Somatostatin / Q000494:pharmacology*
D002147:Calmodulin; D007074:Immunoglobulin G; D011961:Receptors, Fc; D013004:Somatostatin; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium