title: 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.
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 3-12 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.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
authors.forename: Jenny S
authors.initials: JS
authors.lastname: Fusby
authors.forename: Michele D
authors.initials: MD
authors.lastname: Kassmeier
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Palmer
authors.forename: Greg A
authors.initials: GA
authors.lastname: Perry
authors.forename: Dirk K
authors.initials: DK
authors.lastname: Anderson
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Hackfort
authors.forename: Gwen K
authors.initials: GK
authors.lastname: Alvarez
authors.forename: Diane M
authors.initials: DM
authors.lastname: Cullen
authors.forename: Mohammed P
authors.initials: MP
authors.lastname: Akhter
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Swanson
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D015519:Bone Density / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D001854:Bone Marrow Cells; D016516:CD4-CD8 Ratio; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D026502:LDL-Receptor Related Proteins / Q000172:deficiency / Q000235:genetics; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012907:Smoking / Q000009:adverse effects* / Q000276:immunology; D016540:Smoking Cessation; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D014028:Tobacco Smoke Pollution
chemical_list: D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; D014028:Tobacco Smoke Pollution