title: N-acetylcysteine increases the frequency of bone marrow pro-B/pre-B cells, but does not reverse cigarette smoking-induced loss of this subset.
abstract: BACKGROUND
  We previously showed that mice exposed to cigarette smoke for three weeks exhibit loss of bone marrow B cells at the Pro-B-to-pre-B cell transition, but the reason for this is unclear. The antioxidant N-acetylcysteine (NAC), a glutathione precursor, has been used as a chemopreventive agent to reduce adverse effects of cigarette smoke exposure on lung function. Here we determined whether smoke exposure impairs B cell development by inducing cell cycle arrest or apoptosis, and whether NAC treatment prevents smoking-induced loss of developing B cells.
  
  
  RESULTS
  Groups of normal mice were either exposed to filtered room air or cigarette smoke with or without concomitant NAC treatment for 5 days/week for three weeks. Bone marrow B cell developmental subsets were enumerated, and sorted pro-B (B220(+)CD43(+)) and pre-B (B220(+)CD43(-)) cell fractions were analyzed for cell cycle status and the percentage of apoptotic cells. We find that, compared to sham controls, smoke-exposed mice have ∼60% fewer pro-B/pre-B cells, regardless of NAC treatment. Interestingly, NAC-treated mice show a 21-38% increase in total bone marrow cellularity and lymphocyte frequency and about a 2-fold increase in the pro-B/pre-B cell subset, compared to sham-treated controls. No significant smoking- or NAC-dependent differences were detected in frequency of apoptotic cells or the percentage cells in the G1, S, or G2 phases of the cycle.
  
  
  CONCLUSIONS
  The failure of NAC treatment to prevent smoking-induced loss of bone marrow pre-B cells suggests that oxidative stress is not directly responsible for this loss. The unexpected expansion of the pro-B/pre-B cell subset in response to NAC treatment suggests oxidative stress normally contributes to cell loss at this developmental stage, and also reveals a potential side effect of therapeutic administration of NAC to prevent smoking-induced loss of lung function.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, United States of America.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Palmer
authors.forename: Michele D
authors.initials: MD
authors.lastname: Kassmeier
authors.forename: James
authors.initials: J
authors.lastname: Willcockson
authors.forename: Mohammed P
authors.initials: MP
authors.lastname: Akhter
authors.forename: Diane M
authors.initials: DM
authors.lastname: Cullen
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Swanson
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000111:Acetylcysteine