Modulatory effects of N-acetylcysteine on human eosinophil apoptosis

¹ Dept of Pharmacology, University of Valencia, Valencia, Spain
² Dept of Pharmacology, University of Valencia, Valencia, Spain; and Research Foundation, Consortium University General Hospital, Valencia, Spain
³ Dept of Medicine, University of Valencia, Valencia, Spain; and Service of Pneumology, Consortium University General Hospital, Valencia, Spain
⁴ Service of Pneumology, Consortium University General Hospital, Valencia, Spain
⁵ Dept of Pharmacology, University of Valencia, Valencia, Spain; and Clinical Pharmacology Unit, University Clinic Hospital, Valencia, Spain

	Abstract

Eosinophils are oxidant-sensitive cells considered relevant in allergic inflammation. We aimed to study the effects of the antioxidant N-acetylcysteine (NAC) on constitutive and cytokine-delayed apoptosis in human isolated eosinophils.

Human eosinophils were purified from blood of healthy donors by a magnetic separation system. Apoptosis and cellular glutathione were assessed by cytofluorometric analysis, and NF-B binding activity by electrophoresis mobility shift assay.

The rate of spontaneous apoptosis of human eosinophils after 24 h of culture as assessed by annexin V positive staining was 48.2±1.4% (n=5). GM-CSF (10 ng ml^-1) decreased apoptosis to 19.4±1.8% (n=5; P<0.05). NAC (5mM) inhibited spontaneous apoptosis (33.6±2.7%, n=5, P<0.05) but augmented apoptosis in the presence of GM-CSF (30.9±1.5%; n=5; P<0.05). NAC (5mM) also increased apoptosis rate in presence of TNF- (10 ng ml^-1) and interleukin-5 (5 ng ml^-1). NAC (5mM) increased eosinophil glutathione content. The increase in eosinophil NF-B binding activity induced by GM-CSF and TNF- was suppressed by NAC.

In conclusion, NAC modulates eosinophil apoptosis by inhibiting constitutive apoptosis but reversing the survival effect produced by inflammatory cytokines in human eosinophils.

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