N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism.

The effect of N-acetylcysteine (NAC) on human neutrophil and monocyte cell viability, chemotaxis, oxygen consumption and chemiluminescence was studied. It was found that NAC at concentrations higher than 3 X 10(-2) M resulted in neutrophil and monocyte cytotoxicity. The studies on the effect of NAC on neutrophil and monocyte chemotaxis showed that NAC inhibited chemotaxis of both cell types in a concentration dependent manner. NAC at 3 X 10(-2) M inhibited chemotaxis of both cell types by about 50% and at 10(-1) M inhibited PMN chemotaxis by 95% and MNL chemotaxis by 85%. The studies on the effect of NAC on neutrophil chemiluminescence demonstrated that NAC at concentrations of 1.5 X 10(-2) M, or higher, inhibited the response of the activated cells totally. When pH adjusted NAC or Mucomyst was used the inhibition was observed with higher concentrations of the drug (1.5 X 10(-1) M). NAC exhibited a similar pattern of inhibition on monocyte chemiluminescence response. These findings demonstrate that NAC, at concentrations obtainable in vivo by inhalation, impairs the chemotaxis and generation of oxygen radicals by human phagocytic cells. This property of NAC could have important implications concerning the prevention of tissue damage caused by these cells in inflammatory areas.

[1]  H. Carp,et al.  Lung injury induced by leukocytic proteases. , 1979, The American journal of pathology.

[2]  A. Kharazmi,et al.  Interaction of Pseudomonas aeruginosa alkaline protease and elastase with human polymorphonuclear leukocytes in vitro , 1984, Infection and immunity.

[3]  A. Kharazmi,et al.  Elastase from polymorphonuclear leucocytes: a regulatory enzyme in immune complex disease. , 1986, Clinical and experimental immunology.

[4]  HERMAN W. REAS The Use of N-Acetylcysteine in the Treatment of Cystic Fibrosis , 1963, Southern medical journal.

[5]  P. Ward,et al.  Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. , 1982, The American journal of pathology.

[6]  J. Feix,et al.  Chlorpromazine inhibits neutrophil chemotaxis beyond the chemotactic receptor-ligand interaction. , 1984, The Journal of infectious diseases.

[7]  R. Rogers,et al.  Adult respiratory-distress syndrome: changing concepts of lung injury and repair. , 1982, The New England journal of medicine.

[8]  E. Mitchell,et al.  Controlled trial of oral N‐acetylcysteine in cystic fibrosis , 1982, Australian paediatric journal.

[9]  A. Gazzaniga,et al.  Toxicological, pharmacokinetic and metabolic studies on acetylcysteine. , 1980, European journal of respiratory diseases. Supplement.

[10]  A. Kharazmi,et al.  In vitro modulation of human neutrophil chemotaxis by cis(Z)- and trans(E)-clopenthixol, and chlorpromazine. , 2009, Acta pathologica, microbiologica, et immunologica Scandinavica. Section C, Immunology.

[11]  J. Maddock Biological properties of acetylcysteine: assay development and pharmacokinetic studies. , 1980, European journal of respiratory diseases. Supplement.

[12]  W. Crosby,et al.  Cytochemical identification of monocytes and granulocytes. , 1971, American journal of clinical pathology.

[13]  G. Boman,et al.  Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases. , 1983, European journal of respiratory diseases.

[14]  Y. Ozaki,et al.  Enhancement of chemiluminescence of the neutrophils by low concentrations of trifluoperazine. , 1984, Biochemical and biophysical research communications.

[15]  V. Ferrans,et al.  Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage. , 1979, The American journal of pathology.

[16]  R. C. Kory,et al.  Sputum liquefying agents: a comparative in vitro evaluation. , 1969, Journal of Laboratory and Clinical Medicine.

[17]  G. Bernard,et al.  Effect of N-acetylcysteine on the pulmonary response to endotoxin in the awake sheep and upon in vitro granulocyte function. , 1984, The Journal of clinical investigation.

[18]  A. Kharazmi,et al.  Demonstration of neutrophil chemotactic activity in the sputum of cystic fibrosis patients with Pseudomonas aeruginosa infection , 1986, European journal of clinical investigation.

[19]  G. Koch,et al.  Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment. , 1981 .