title: The influence of nicotine on granulocytic differentiation - inhibition of the oxidative burst and bacterial killing and increased matrix metalloproteinase-9 release.
abstract: BACKGROUND
  Neutrophils leave the bone marrow as terminally differentiated cells, yet little is known of the influence of nicotine or other tobacco smoke components on neutrophil differentiation. Therefore, promyelocytic HL-60 cells were differentiated into neutrophils using dimethylsulfoxide in the presence and absence of nicotine (3-(1-methyl-2-pyrrolidinyl) pyridine). Differentiation was evaluated over 5 days by monitoring terminal differentiation markers (CD11b expression and formazan deposition); cell viability, growth phase, kinetics, and apoptosis; assessing cellular morphology and ultrastructure; and conformational changes to major cellular components. Key neutrophil effector functions (oxidative burst, bacterial killing, matrix metalloproteinase release) were also examined.
  
  
  RESULTS
  Nicotine increased the percentage of cells in late differentiation phases (metamyelocytes, banded neutrophils and segmented neutrophils) compared to DMSO alone (p < 0.05), but did not affect any other marker of neutrophil differentiation examined. However, nicotine exposure during differentiation suppressed the oxidative burst in HL-60 cells (p < 0.001); inhibited bacterial killing (p < 0.01); and increased the LPS-induced release of MMP-9, but not MMP-2 (p < 0.05). These phenomena may be alpha-7-acetylcholine nicotinic receptor-dependent. Furthermore, smokers exhibited an increased MMP-9 burden compared to non-smokers in vivo (p < 0.05).
  
  
  CONCLUSIONS
  These findings may partially explain the known increase in susceptibility to bacterial infection and neutrophil-associated destructive inflammatory diseases in individuals chronically exposed to nicotine.
authors.affiliation: Department of Oral Biology, University of Manitoba, Winnipeg, Canada. xmq075@hotmail.com
authors.forename: Minqi
authors.initials: M
authors.lastname: Xu
authors.forename: James E
authors.initials: JE
authors.lastname: Scott
authors.forename: Kan-Zhi
authors.initials: KZ
authors.lastname: Liu
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Bishop
authors.forename: Diane E
authors.initials: DE
authors.lastname: Renaud
authors.forename: Richard M
authors.initials: RM
authors.lastname: Palmer
authors.forename: Abdel
authors.initials: A
authors.lastname: Soussi-Gounni
authors.forename: David A
authors.initials: DA
authors.lastname: Scott
mesh_terms: D001433:Bacteriolysis / Q000187:drug effects / Q000502:physiology; D002038:Bungarotoxins / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D016130:Immunophenotyping; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology / Q000502:physiology*; D009538:Nicotine / Q000633:toxicity*; D016966:Porphyromonas gingivalis; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects / Q000502:physiology; D012907:Smoking / Q000009:adverse effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D002038:Bungarotoxins; C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D020780:Matrix Metalloproteinase 9