The effect of paraquat on the aerobic metabolism of rabbit alveolar macrophages and lung fibroblasts

Abstract

In this study the effects of paraquat on the aerobic metabolism and viability of isolated rabbit alveolar macrophages and lung fibroblasts were investigated, and compared with the effects of other known metabolic inhibitors, i.e. sodium fluoride (NaF) and potassium cyanide (KCN). The manometrically and polarographically determined endogenous oxygen consumption of lavaged alveolar macrophages compared very well (180,9 +/- 35,8 and 169,3 +/- 26,8 nmol per 10(6) viable cells per hour respectively). Exogenous glucose (10 mM) and autologous serum (1:3 v/v) added to the medium had no significant effect on the basal respiration rate. The mean cell protein content, determined by the micro-Kjeldahl and Lowry techniques, amounted to 242,6 +/- 37,6 microgram/10(6) macrophages. Paraquat (2 mM), like NaF (20mM) and KCN (5 mM), decreased the viability of the macrophages far less than it did the oxygen utilization of the viable cells, and resulted in an 80% inhibition of oxygen uptake. In contrast, paraquat (1 mM) induced a marked stimulation (230%) of the cyanide-insensitive respiration of alveolar macrophages. The concentrations of paraquat (nmol/10(3) cells) which reduce macrophage metabolism to almost zero were virtually non-toxic to fibroblasts, as measured by their oxygen consumption.