S-carboxymethylcysteine inhibits neutrophil activation mediated by N-formyl-methionyl-leucyl-phenylalanine.
In this study, the possible mechanisms of action for the inhibitory effects of S-carboxymethylcysteine on the activation of human neutrophils by N-formyl-methionyl-leucyl-phenylalanine (FMLP) were investigated. Preincubation of neutrophils with more than 10 microg/ml of S-carboxymethylcysteine was found to impair neutrophil chemotactic activity toward FMLP, and to inhibit FMLP-mediated neutrophil adherence to pulmonary vascular endothelial cells. Preincubation of neutrophils with 10 and 100 microg/ml of S-carboxymethylcysteine decreased in the production of inositol 1,4,5-triphosphate (IP(3)) and diacylglycerol in neutrophils stimulated with FMLP, respectively. Preincubation of neutrophils with S-carboxymethylcysteine did not affect the cellular cyclic AMP (cAMP) levels in neutrophils stimulated with FMLP. S-carboxymethylcysteine inhibited the enzymatic activity of phosphatidyl inositol-specific phospholipase C in vitro in a concentration-dependent manner. These findings indicate that S-carboxymethylcysteine attenuates FMLP-stimulated neutrophil activation at least in part by inhibiting phosphatidyl inositol-specific phospholipase C-mediated signal transduction.
Ishii
Yukio
Y
Department of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Ten-nohdai, Tsukuba, Ibaraki 305-0006, Japan. ishii-y@md.tsukuba.ac.jp
Kimura
Toru
T
Morishima
Yuko
Y
Mochizuki
Mie
M
Nomura
Akihiro
A
Sakamoto
Tohru
T
Uchida
Yoshiyuki
Y
Sekizawa
Kiyohisa
K
D002233:Carbocysteine / Q000494:pharmacology*; D002448:Cell Adhesion; D002474:Cell-Free System / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism
C011439:1,2-diacylglycerol; D004075:Diglycerides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002233:Carbocysteine; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins