Enhancement of natural killer cell activity in septic shock patients by a mixture of the calcium ionophore A23187 and the phorbol ester TPA: in vitro studies.
Preincubation of peripheral blood lymphocytes from drug-free, healthy volunteers with a mixture of the calcium ionophore A23187 (Io) and the phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) consistently resulted in a significant enhancement (dose-dependent; maximum immunostimulation obtained with the Io + TPA final mixture concentration of 10 uM + 250 ng/ml, respectively) of natural killer cell activity (NKCA) (n = 8; mean +/- SD of 16.8 +/- 8.9 and 52.0 +/- 18.0, paired Student's t-test p < 0.005; effector-to-target cell ratio of 30:1). Results from the same protocol, but using samples from septic shock patients followed a similar trend; however, and perhaps reflecting the significantly lower baseline NKCA in this group of individuals (n = 7), the mean value reached for this cellular immune function after incubation with Io + TPA was significantly lower than that of the treated controls' group (mean +/- SD of 19.8 +/- 11.6 and 52.0 +/- 18.0, respectively, Student's t-test p < 0.005). As expected from the role of calcium in the activation of NKCA, incubation with the Io significantly increased baseline NKCA, which was largely unchanged by TPA. Expression of the CD56+ and CD16+ phenotypes in septic shock patients did not correlate directly with NKCA, suggesting that this condition may be associated with changes in the function rather than the quantity of these cellular markers.(ABSTRACT TRUNCATED AT 250 WORDS)
Puente
J
J
Department of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, Univ. of Chile, Santiago.
Carvajal
T
T
Parra
S
S
Miranda
D
D
Sepulveda
C
C
Wolf
M E
ME
Mosnaim
A D
AD
D000328:Adult; D000001:Calcimycin / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012772:Shock, Septic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology* / Q000627:therapeutic use
D004338:Drug Combinations; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate