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).
Kamal
A M
AM
Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Charing Cross Hospital, London, UK.
Tetley
T D
TD
Witherden
I R
IR
Smith
S F
SF
D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000906:Antibodies / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009500:Neutralization Tests; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D051381:Rats; D017208:Rats, Wistar
D017305:Annexin A1; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D008070:Lipopolysaccharides; D008934:Mitogens; D010446:Peptide Fragments; D010455:Peptides; C096153:annexin A1 peptide (2-26); D009569:Nitric Oxide; D003907:Dexamethasone