Cigarette smoke-induced effects on bone marrow B-cell subsets and CD4 +:CD8+ T-cell ratios are reversed by smoking cessation: Influence of bone mass on immune cell response to and recovery from smoke exposure

Jenny S. Fusby, Michele D. Kassmeier, Victoria L. Palmer, Greg A. Perry, Dirk K. Anderson, Bryan T. Hackfort, Gwen K. Alvarez, Diane M. Cullen, Mohammed P. Akhter, Patrick C. Swanson

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Cigarette smoking adversely affects the immune system, and is a risk factor for developing osteoporosis. How smoking contributes to osteoporosis is unclear, but since lymphocytes help maintain bone homeostasis and lymphocyte depletion results in bone loss, one potential mechanism for how smoke exposure promotes osteoporosis is by reducing bone marrow lymphocytes. Since the risk for developing osteoporosis is reportedly greater in smokers with polymorphisms in LRP5, a gene involved in canonical Wnt signaling that regulates bone metabolism, smoking-induced effects on lymphocytes may be influenced by Lrp5 functionality. To test these possibilities, we examined how the duration and cessation of cigarette smoke exposure affects lymphocyte distribution and function in normal mice and mice predisposed to low or high bone mass due to disruption or mutation of Lrp5. We find that, independent of genotype, mice exposed to cigarette smoke for 312 weeks showed a significant reduction in bone marrow B220 +CD43- B cells and splenic transitional T1 B cells, and exhibited a splenic CD4+:CD8+ T-cell ratio that was skewed toward CD8+ T cells. Smoke exposure had little or no effect on other lymphocyte subsets or on lymphocyte function ex vivo. Interestingly, these differences were no longer apparent after 6 weeks without smoke exposure, except in mice with high bone mass where bone marrow B220+CD43- B cells failed to fully recover. These data provide the first evidence that smoke exposure reduces bone marrow B cells, providing a plausible mechanism for how smoking contributes to osteoporosis.

Original languageEnglish (US)
Pages (from-to)785-796
Number of pages12
JournalInhalation Toxicology
Volume22
Issue number9
DOIs
StatePublished - Aug 2010

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

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