Heme oxygenase-1 prevents smoke induced B-cell infiltrates: a role for regulatory T cells?
BACKGROUND
Smoking is the most important cause for the development of COPD. Since not all smokers develop COPD, it is obvious that other factors must be involved in disease development. We hypothesize that heme oxygenase-1 (HO-1), a protective enzyme against oxidative stress and inflammation, is insufficiently upregulated in COPD. The effects of HO-1 modulation on cigarette smoke induced inflammation and emphysema were tested in a smoking mouse model.


METHODS
Mice were either exposed or sham exposed to cigarette smoke exposure for 20 weeks. Cobalt protoporphyrin or tin protoporphyrin was injected during this period to induce or inhibit HO-1 activity, respectively. Afterwards, emphysema development, levels of inflammatory cells and cytokines, and the presence of B-cell infiltrates in lung tissue were analyzed.


RESULTS
Smoke exposure induced emphysema and increased the numbers of inflammatory cells and numbers of B-cell infiltrates, as well as the levels of inflammatory cytokines in lung tissue. HO-1 modulation had no effects on smoke induced emphysema development, or the increases in neutrophils and macrophages and inflammatory cytokines. Interestingly, HO-1 induction prevented the development of smoke induced B-cell infiltrates and increased the levels of CD4+CD25+ T cells and Foxp3 positive cells in the lungs. Additionally, the CD4+CD25+ T cells correlated positively with the number of Foxp3 positive cells in lung tissue, indicating that these cells were regulatory T cells.


CONCLUSIONS
These results support the concept that HO-1 expression influences regulatory T cells and indicates that this mechanism is involved in the suppression of smoke induced B-cell infiltrates. The translation of this interaction to human COPD should now be pursued.
Brandsma
Corry-Anke
CA
Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, P,O, Box 30,001, 9700 RB, Groningen, The Netherlands. c.a.brandsma@path.umcg.nl
Hylkema
Machteld N
MN
van der Strate
Barry W A
BW
Slebos
Dirk-Jan
DJ
Luinge
Marjan A
MA
Geerlings
Marie
M
Timens
Wim
W
Postma
Dirkje S
DS
Kerstjens
Huib A M
HA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D002450:Cell Communication; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D016014:Linear Models; D051379:Mice; D008805:Mice, Inbred A; D011336:Probability; D011656:Pulmonary Emphysema / Q000201:enzymology* / Q000276:immunology* / Q000517:prevention & control; D011897:Random Allocation; D012016:Reference Values; D012906:Smoke; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016207:Cytokines; D012906:Smoke; D051547:Heme Oxygenase-1