Phenanthrene decreases neutrophil function by disrupting intracellular redox balance

Abstract

The aim of the present work was to evaluate whether the treatment of human neutrophils with phenanthrene (PHN) can alter the phagocytic and microbicidal capacity of these cells by causing a disruption in redox balance. Peripheral neutrophils from healthy subjects were treated for up to 24 h with increasing concentrations of phenanthrene. Phagocytic/microbicidal activities, antioxidant enzymes, oxidative lesions (thiobarbituric acid-reactive substances and protein thiol and carbonyl groups) and redox signaling compounds (intracellular Ca(2+), superoxide, hydrogen peroxide and nitric oxide) were monitored on neutrophils exposed to 10 microg PHN ml(-1). Cell viability decreased abruptly at PHN concentrations above 10 microg ml(-1) (LC50 = 20.86 +/- 0.51 microg ml(-1) and p-sigmoidal slope = 19.88 +/- 10.11). Phagocytic and microbicidal capacities were decreased by 60 and 82%, respectively. Substantial increases in total-/Mn-SOD, catalase, glutathione peroxidase and glutathione reductase activities (by 61, 15, 87, 245 and 70%, respectively) matched the oxidative injury obtained in TBARS (2.5-fold higher) and protein thiol (54% lower). Diminished productions of superoxide by 18% and hydrogen peroxide by 29% were observed in association to exacerbated calcium (27%) and nitric oxide (63%) levels. The data indicate that phenanthrene might be associated with substantial reduction in human neutrophil functions due to severe intracellular redox imbalances.