PROTECTION BY L-2-OXOTHIAZOLIDINE-4-CARBOXYLIC ACID OF HYDROGEN PEROXIDE-INDUCED CD3-ZETA AND CD16-ZETA CHAIN DOWN-REGULATION IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTES AND LYMPHOKINE-ACTIVATED KILLER-CELLS
Mm. Corsi et al., PROTECTION BY L-2-OXOTHIAZOLIDINE-4-CARBOXYLIC ACID OF HYDROGEN PEROXIDE-INDUCED CD3-ZETA AND CD16-ZETA CHAIN DOWN-REGULATION IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTES AND LYMPHOKINE-ACTIVATED KILLER-CELLS, Biochemical pharmacology, 56(5), 1998, pp. 657-662
We investigated whether L-2-oxothiazolidine-4-carboxylic acid (OTC) [i
n the form of Procysteine(R), kindly donated by Transcend Therapeutics
] could protect peripheral blood lymphocytes (PBL) and lymphokine-acti
vated killer (LAK) cells from CD3 zeta and CD16 zeta chain down-regula
tion induced by H2O2 produced by lipopolysaccharide (LPS)-activated au
tologous monocytes. OTC is known to enhance glutathione production in
cells in which glutathione was depleted by reactive oxygen species. Ou
r data showed that OTC induced a significant increase in CD3 zeta and
CD16 zeta chain expression in peripheral blood lymphocytes and LAK cel
ls, respectively, pretreated for 12 hr at 37 degrees. Moreover, OTC si
gnificantly protected peripheral blood lymphocytes and LAK against dec
reased zeta chain expression induced by lipopolysaccharide-activated m
onocytes or the addition of H2O2 to the culture medium. Our experiment
s thus suggested that alterations in signal-transducing molecules, suc
h as decreased CD3 zeta and CD16 zeta expression observed in cytotoxic
T lymphocytes and LAK cells in response to oxidative stress, could be
prevented by the use of OTC. (C) 1998 Elsevier Science Inc.