N-acetylcysteine causes a transient stimulation of neutrophil migration.
Random migration of rabbit peritoneal neutrophils was enhanced in a chemokinetic way by N-acetylcysteine (NAC) in a small concentration range (10-400 microM). The enhancement was due to the cysteine moiety in the molecule, because cysteine equally caused a stimulation of random migration. The stimulating effect of NAC or cysteine largely disappeared when cells were preincubated with NAC or cysteine for 30 min before submission to chemotaxis, indicating that desensitization occurs. The stimulating effect of NAC was dependent on extracellular calcium. Because the Ca2+-dependence of migration by electroporated cells differed from that of intact cells, and because calcium channel blockers inhibited the effect of NAC, the calcium-dependent target is probably located inside the cell rather than on the cell surface. In contrast with fMLP, NAC did not cause an upregulation of CD11b expression of cells in suspension. Inhibitors of guanylate cyclase and of cGMP-dependent protein kinase (G-kinase) inhibited stimulation of migration by NAC, suggesting that cGMP played a decisive role in the stimulatory effect of NAC.
Elferink
J G
JG
Department of Medical Biochemistry, University of Leiden, The Netherlands.
de Koster
B M
BM
D000111:Acetylcysteine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003545:Cysteine / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D010529:Peritoneal Cavity / Q000166:cytology; D011817:Rabbits
D016166:Free Radical Scavengers; D016177:Macrophage-1 Antigen; D009240:N-Formylmethionine Leucyl-Phenylalanine; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D003545:Cysteine; D002118:Calcium; D000111:Acetylcysteine