NITRIC-OXIDE SYNTHESIS BY RAT PLEURAL MESOTHELIAL CELLS - INDUCTION BY GROWTH-FACTORS AND LIPOPOLYSACCHARIDE

The purpose of this study was to determine if certain growth factors a nd bacterial products induce pleural mesothelial cells (PMC) to produc e nitric oxide (NO). Confluent monolayers of rat PMC were exposed to e pidermal growth factor (EGF), platelet-derived growth factor (PDGF), o r lipopolysaccharide (LPS) individually and in various combinations fo r 24-72 h. Concentrations of nitrite and nitrate were quantified and u sed as an indirect measure of NO production. LPS stimulation resulted in a significant increase in nitrite/nitrate concentration, but neithe r EGF nor PDGF alone or combined had any significant effect relative t o control. However, LPS combined with either EGF or PDGF caused a sign ificant increase in nitrite/nitrate concentration relative to LPS alon e and growth factor alone. The highest level of nitrite/nitrate concen tration was observed with the triple combination of LPS, EGF, and PDGF . Nitrite/nitrate accumulation was significantly increased at 24 h by all combinations, and continued to increase, with the highest concentr ation observed after 72 h of exposure. Nitrite/nitrate production was significantly inhibited by N-G-nitro-L-arginine methyl ester and this inhibition was reversed by tile addition of L-arginine, suggesting tha t nitrite and nitrate were derived from the L-arginine-dependent forma tion of NO. These data indicate that PMC can be induced to produce rel atively large amounts of NO in response to growth factors combined wit h LPS.