Cigarette smoke enhances chemotaxis via acetylation of proline-glycine-proline

Front Biosci (Elite Ed). 2012 Jun 1;4:2402-9. doi: 10.2741/e552.


Several chronic lung diseases have been linked to cigarette smoking (Chronic Obstructive Pulmonary Disease (COPD), and cancer are associated with increased tobacco use). We recently described a collagen fragment, proline-glycine-proline (PGP), chemotactic for neutrophils, that appears to play a role in COPD, cystic fibrosis, and bronchiolitis obliterans syndrome. PGP can exist in either its native or acetylated form (NAcPGP), although the mechanism of N-terminal-acetylation remains unknown. This work investigates the possibility that cigarette smoke (CS) and its components acetylate PGP, describing a possible mechanism for some of the chronic inflammation seen in tobacco-associated disease. CSE and CSC (3.56 and 12.38 ng/ml NAcPGP respectively, p less than 0.01) and its components (acrolein, acetaldehyde, and methyl glyoxal) acetylated PGP (0.51, 1.03, and 0.23 ng/ml NAcPGP, p less than 0.01). Both N-acetyl-cysteine and carbocysteine (scavengers of reactive aldehydes) blocked chemical acetylation of PGP by CS (100 percent and 97 percent inhibition, respectively, p less than 0.01). NAcPGP is more chemoattractive to neutrophils, and less susceptible to degradation by Leukotriene-A4-Hydrolase (detected in the lung). These experiments propose a mechanism for the increased neutrophil recruitment seen in smoking-associated lung diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetylcysteine / pharmacology
  • Carbocysteine / pharmacology
  • Chemotaxis, Leukocyte*
  • Humans
  • Neutrophils / cytology
  • Oligopeptides / metabolism*
  • Proline / analogs & derivatives*
  • Proline / metabolism
  • Smoke*
  • Tobacco*


  • Oligopeptides
  • Smoke
  • prolyl-glycyl-proline
  • Carbocysteine
  • Proline
  • Acetylcysteine