Protection by L-2-oxothiazolidine-4-carboxylic acid of hydrogen peroxide-induced CD3zeta and CD16zeta chain down-regulation in human peripheral blood lymphocytes and lymphokine-activated killer cells.
We investigated whether L-2-oxothiazolidine-4-carboxylic acid (OTC) [in the form of Procysteine, kindly donated by Transcend Therapeutics] could protect peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells from CD3zeta and CD16zeta chain down-regulation induced by H2O2 produced by lipopolysaccharide (LPS)-activated autologous monocytes. OTC is known to enhance glutathione production in cells in which glutathione was depleted by reactive oxygen species. Our data showed that OTC induced a significant increase in CD3zeta and CD16zeta chain expression in peripheral blood lymphocytes and LAK cells, respectively, pretreated for 12 hr at 37 degrees. Moreover, OTC significantly protected peripheral blood lymphocytes and LAK against decreased zeta chain expression induced by lipopolysaccharide-activated monocytes or the addition of H2O2 to the culture medium. Our experiments thus suggested that alterations in signal-transducing molecules, such as decreased CD3zeta and CD16zeta expression observed in cytotoxic T lymphocytes and LAK cells in response to oxidative stress, could be prevented by the use of OTC.
Corsi
M M
MM
Institute of General Pathology, Faculty of Medicine, University of Milan, Italy. mmcorsi@imiucca.csi.unimi.it
Maes
H H
HH
Wasserman
K
K
Fulgenzi
A
A
Gaja
G
G
Ferrero
M E
ME
D017252:CD3 Complex / Q000097:blood*; D019610:Cytoprotection; D015536:Down-Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000097:blood; D011948:Receptors, Antigen, T-Cell / Q000097:blood; D017452:Receptors, IgG / Q000097:blood*; D015398:Signal Transduction / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D017252:CD3 Complex; D008070:Lipopolysaccharides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D017452:Receptors, IgG; D013844:Thiazoles; D053778:Thiazolidines; D006861:Hydrogen Peroxide; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid