Reduction of nitric oxide release from alveolar macrophages by a lipocortin peptide.

Nitric oxide (NO), produced by alveolar macrophages (AM) is used as a marker of respiratory tract inflammation. Lipocortin 1 (Lc-1) is an anti-inflammatory, glucocorticoid-inducible protein. The current aims were to determine whether (a) an Lc-1-derived peptide, Ac2-26, inhibited lipopolysaccharide (LPS)-induced NO release by primary AM in vitro and (b) the inhibitory action of dexamethasone was Lc-1-dependent. LPS treatment stimulated NO release from rat AM. Ac2-26 had little effect on unstimulated release, but suppressed LPS-stimulated release at concentrations > or =320 nM (320 nM, 10 +/- 3%; 3.2 microM, 15 +/- 3%; 32 microM, 27 +/- 4% NO inhibited, mean +/- SEM, n = 6). Inhibition by dexamethasone of NO release was unaffected by neutralizing anti-Lc-1 indicating that this action is Lc-1-independent in primary AM. Nevertheless inhibition of NO release by Ac2-26 (80 microM) was similar to that of 1 microM dexamethasone (Ac2-26, 40 +/- 6%; dexamethasone, 48 +/- 6% NO inhibited, mean +/- SEM, n = 6).