Heme oxygenase-1 prevents smoke induced B-cell infiltrates: a role for regulatory T cells?

Corry-Anke Brandsma,Dirk-Jan Slebos,Dirkje S Postma,Barry Wa Van Der Strate,Wim Timens,Huib Am Kerstjens,Marie Geerlings,Marjan A Luinge,Machteld N Hylkema

doi:10.1186/1465-9921-9-17

Corry-Anke Brandsma, Dirk-Jan Slebos + Show 7 more

Open Access

https://doi.org/10.1186/1465-9921-9-17

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Abstract

BackgroundSmoking 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.MethodsMice 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.ResultsSmoke 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.ConclusionThese 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.

Highlights

Smoking is the most important cause for the development of Chronic obstructive pulmonary disease (COPD)
HO1 modulation had no effects on smoke induced emphysema development, or the increases in neutrophils and macrophages and inflammatory cytokines
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. These results support the concept that heme oxygenase-1 (HO-1) expression influences regulatory T cells and indicates that this mechanism is involved in the suppression of smoke induced B-cell infiltrates

Summary

Introduction

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 and others have found oligoclonal T- and B cells in the lungs of COPD patients suggesting an antigen driven immune response [3,4]. These T-and B cells are aggregated in lymphoid infiltrates. Similar infiltrates have been shown in the lungs of mice chronically exposed to cigarette smoke [3]. We hypothesize that these lymphoid infiltrates contribute to the development and/or persistence of the inflammatory response in COPD [3]

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