Inhibition of human serum complement activity by diisopropylfluorophosphate and selected anticholinesterase insecticides

Abstract

Activation of the human complement (C′) system, a major line of defense against infections, requires the participation of serine esterases. Since the widely used anticholinesterase insecticides inhibit serine esterases, the present study evaluated potencies of carbaryl, carbofuran, dichlorvos, and paraoxon to inhibit C′ activities of a panel of normal human sera. C′-mediated lysis of sheep red cells was measured with a modified assay (1) incorporating suboptimal concentrations of sensitizing antibody and (2) exhibiting increased sensitivity to serine esterase inhibitors. Test chemicals were added to diluted sera 2 hr prior to incorporation into C′ reaction mixtures. Potencies to inhibit C′ and serum cholinesterase (CHE) were compared to potencies of diisopropylfluorophosphate (DFP), a potent serine esterase inhibitor and a standard probe for C′ esterases. At 0.5 to 3.0 m m, carbaryl, carbofuran, dichlorvos, and DFP produced a dose-dependent inhibition of lysis, whereas paraoxon was not inhibitory. On a molar basis, carbaryl was three times more potent than DFP, and inhibited lysis 15–25 and 26–45% at 1.0 and 3.0 m m, respectively. Carbofuran, dichlorvos, and DFP were equipotent. Mean IC50's for inhibition of CHE (a marker for occupational exposure to organophosphates and carbamates) by DFP, paraoxon, dichlorvos, carbofuran, and carbaryl were 1.0 × 10 −8, 4.1 × 10 −8, 1.0 × 10 −7, 3.3 × 10 −6, and 1.8 × 10 −5 m, respectively. Potencies of the insecticides to inhibit CHE did not predict absolute or relative potencies to inhibit serum C′ activity.