Cigarette smoke enhances chemotaxis via acetylation of proline-glycine-proline.
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.
Department of Medicine, University of Alabama at Birmingham 1918 University Blvd., Birmingham, AL 35294, USA.
Matthew Thomas
MT
Hardison
Michael David
MD
Brown
Robert James
RJ
Snelgrove
James Edwin
JE
Blalock
Patricia
P
Jackson
D000107:Acetylation; D000111:Acetylcysteine / Q000494:pharmacology; D002233:Carbocysteine / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D006801:Humans; D009504:Neutrophils / Q000166:cytology; D009842:Oligopeptides / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives* / Q000378:metabolism; D012906:Smoke; D014026:Nicotiana
D009842:Oligopeptides; D012906:Smoke; C113164:prolyl-glycyl-proline; D002233:Carbocysteine; D011392:Proline; D000111:Acetylcysteine