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 Swanson

Research output: Contribution to journalArticle

36 Citations (Scopus)

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

Fingerprint

B-Lymphocyte Subsets
T-cells
Smoking Cessation
Smoke
Tobacco Products
Bone Marrow Cells
Lymphocytes
Bone
Osteoporosis
Cells
T-Lymphocytes
Bone and Bones
Recovery
Smoking
B-Lymphocytes
Bone Marrow
Lymphocyte Depletion
B-Lymphoid Precursor Cells
Lymphocyte Subsets
Immune System

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

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

In: Inhalation Toxicology, Vol. 22, No. 9, 2010, p. 785-796.

Research output: Contribution to journalArticle

Fusby, Jenny S. ; Kassmeier, Michele D. ; Palmer, Victoria L. ; Perry, Greg A. ; Anderson, Dirk K. ; Hackfort, Bryan T. ; Alvarez, Gwen K. ; Cullen, Diane M. ; Akhter, Mohammed P. ; Swanson, Patrick. / 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. In: Inhalation Toxicology. 2010 ; Vol. 22, No. 9. pp. 785-796.
@article{4fc1cc4be0ed4110aa59a6848787ba38,
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 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.",
author = "Fusby, {Jenny S.} and Kassmeier, {Michele D.} and Palmer, {Victoria L.} and Perry, {Greg A.} and Anderson, {Dirk K.} and Hackfort, {Bryan T.} and Alvarez, {Gwen K.} and Cullen, {Diane M.} and Akhter, {Mohammed P.} and Patrick Swanson",
year = "2010",
doi = "10.3109/08958378.2010.483258",
language = "English",
volume = "22",
pages = "785--796",
journal = "Inhalation Toxicology",
issn = "0895-8378",
publisher = "Informa Healthcare",
number = "9",

}

TY - JOUR

T1 - Cigarette smoke-induced effects on bone marrow B-cell subsets and CD4 +

T2 - CD8+ T-cell ratios are reversed by smoking cessation: Influence of bone mass on immune cell response to and recovery from smoke exposure

AU - Fusby, Jenny S.

AU - Kassmeier, Michele D.

AU - Palmer, Victoria L.

AU - Perry, Greg A.

AU - Anderson, Dirk K.

AU - Hackfort, Bryan T.

AU - Alvarez, Gwen K.

AU - Cullen, Diane M.

AU - Akhter, Mohammed P.

AU - Swanson, Patrick

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77954808261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954808261&partnerID=8YFLogxK

U2 - 10.3109/08958378.2010.483258

DO - 10.3109/08958378.2010.483258

M3 - Article

VL - 22

SP - 785

EP - 796

JO - Inhalation Toxicology

JF - Inhalation Toxicology

SN - 0895-8378

IS - 9

ER -