THE ROLE OF CARBON-MONOXIDE IN LUCIGENIN-DEPENDENT CHEMILUMINESCENCE OF RAT ALVEOLAR MACROPHAGES

We have investigated the role of carbon monoxide (CO) in lucigenin-dependent chemiluminescence of alveolar macrophages from rat lungs. CO (10 nM to 1 mu M) decreased chemiluminescence of alveolar macrophages in a concentration-dependent fashion. At a concentration of 1 mu M, CO significantly increased intracellular cyclic GMP levels from a control value of 175 +/- 25 fmol/2 x 10(6) cells to 431 +/- 49 fmol/2 x 10(6) cells. Pretreatment of alveolar macrophages with N-G-monomethyl-L-arginine (100 mu M) failed to inhibit CO (1 mu M)-induced decreases in chemiluminescence of alveolar macrophages (3.7 +/- 0.7 cpm X 10(3) in the presence of N-G-monomethyl-L-arginine and 3.4 +/- 0.6 cpm X 10(3) in the absence of N-G-monomethyl-L-arginine) and CO (1 mu M)-induced increases in intracellular cyclic GMP levels (452 +/- 65 fmol/2 X 10(6) cells in the presence of N-G-monomethyl-L-arginine and 419 +/- 58 fmol/2 x 10(6) cells in the absence of N-G-monomethyl-L-arginine). Decreases in chemiluminescence of alveolar macrophages induced by CO (1 mu M) were concentration-dependently inhibited by methylene blue (from 0.1 mu M to 10 mu M). Dibutyryl cyclic GMP (db cyclic GMP) (1 mM) also reduced chemiluminescence of alveolar macrophages (1.5 +/- 0.3 cpm x 10(3) in the presence of db cyclic GMP and 3.6 +/- 0.6 cpm X 10(3) in the absence of db cyclic GMP). In contrast to CO and db cyclic GMP, zinc protoporphyrin-9 (10 nM to 1 mu M), an inhibitor of heme oxygenase potentiated chemiluminescence of alveolar macrophages in a concentration-dependent fashion. Northern blot analysis revealed that alveolar macrophages expressed mRNA of heme oxygenase-1. These results suggest that an endogenous CO-like factor inhibits chemiluminescence of alveolar macrophages via activating guanylate cyclase.