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 an ti-inflammatory, glucocorticoid-inducible protein. The current aims we re to determine whether (a) an Lc-l-derived peptide, Ac2-26, inhibited lipopolysaccharide (LPS)induced NO release by primary AM in vitro and (b) the inhibitory action of dexamethasone was Lc-l-dependent, LPS tr eatment stimulated NO release from rat AM, Ac2-26 had little effect on unstimulated release, but suppressed LPS-stimulated release at concen trations greater than or equal to 320 nM (320 nM, 10 +/- 3%; 3.2 mu M, 15 +/- 3%; 32 mu M, 27 +/- 4% NO inhibited, mean +/- SEM, n = 6), Inh ibition by dexamethasone of NO release was unaffected by neutralizing anti-lc-l indicating that this action is Lc-l-independent in primary A M, Nevertheless inhibition of NO release by Ac2-26 (80 mu M) was simil ar to that of 1 mu M dexamethasone (Ac2-26, 40 +/- 6%; dexamethasone, 48 +/- 6% NO inhibited, mean +/- SEM, n = 6).