RT Journal Article
SR Electronic
T1 Carbocysteine and N-acetyl cysteine inhibit cigarette smoke mediated acetylation of the PMN chemoattractant peptide PGP
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p3854
VO 38
IS Suppl 55
A1 Michael Brown
A1 Matthew Hardison
A1 Edwin Blalock
A1 Patricia Jackson
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p3854.abstract
AB Cigarette smoke contains reactive compounds that result in epithelial damage and stimulate neutrophil chemotaxis, airway invasion, and collagen breakdown. Proline-Glycine-Proline (PGP) is a degradation product of collagen proteolysis. PGP activates neutrophil receptors stimulating further chemotaxis and inflammation.PGP and an N-terminal acetylated PGP (NAcPGP) are elevated in clinical samples of COPD patients and correlate with disease activity. NAcPGP confers increased potency for neutrophil stimulation and bioavailability as leukotriene A4 Hydrolase, responsible for PGP destruction, is incapable of acting on NAcPGP.N-acetyl cysteine (NAC) and carbocysteine (CC) are scavengers of reactive compounds and used as mucolytics in chronic lung diseases. We hypothesize that NAC and/or CC will prevent PGP acetylation by cigarette smoke. These compounds may provide better understanding of targeted therapeutics in cigarette smoking-related lung disease.Cigarette smoke extract (CSE) or condensate (CSC) was prepared and incubated with native PGP +/- NAC or CC. Samples were incubated and analyzed for NAcPGP. NAcPGP concentration was measured with mass spectrometry. This data was repeated in a vapor experiment, where PGP mixed with either NAC or CC was placed in a separate well from cigarette smoke in a 96-well plate and incubated.Our data demonstrate NAcPGP generation by cigarette smoke extract, condensate, and vapor that is inhibited by NAC or CC.Our data support a possible mechanism where reducing compounds such as NAC and CC may diminish lung inflammation in COPD and other chronic lung diseases by inhibiting PGP acetylation thereby facilitating PGP degradation.