ENDOTHELIN-1 DOES NOT PRIME POLYMORPHONUCLEAR LEUKOCYTES FOR ENHANCEDPRODUCTION OF REACTIVE OXYGEN METABOLITES

The in vitro effect of endothelin-1 (ET-1) on the capacity of polymerp honuclear leukocytes (PMNLs) to generate reactive oxygen species (ROS) was investigated. Human PMNLs were separated from healthy volunteers and preincubated for 10 min. at 37 degrees C with varying concentratio ns (10-(7)-10-(12) M) of ET-1. After subsequent stimulation with FMLP (10(-7) M) or opsonized zymosan (0.5 mg/ml) the intra- and extracellul ar generation of ROS was assessed by luminol-amplified chemiluminescen ce, superoxide radical (. O-2(-)) and hydrogen peroxide (H2O2) product ion. Results: ET-1 alone failed to stimulate ROS generation. Neither t he capacity for extracellular generation of oxygen metabolites nor the production of ROS with an intracellular origin was changed after prei ncubation of PMNLs with ET-1. ET-1 did not cause a shift of the . O-2( -)/H2O2 production ratio after stimulation of PMNLs with FMLP. These f indings suggest that ET-1 in vitro does not prime human PMNLs for enha nced production of ROS.