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

Brandsma CA, Hylkema MN, van der Strate BW, Slebos DJ, Luinge MA, Geerlings M, Timens W, Postma DS, Kerstjens HA - Respir. Res. (2008)

Bottom Line: HO-1 modulation had no effects on smoke induced emphysema development, or the increases in neutrophils and macrophages and inflammatory cytokines.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT

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.

Conclusion: 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.

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Related in: MedlinePlus

Emphysema development. Mean linear intercept (LMI) after long term smoke exposure and protoporphyrin treatment. Smoke groups are represented by closed symbols and sham smoke groups by open symbols. * indicates a significant effect of smoke exposure (p < 0.05). There were no interactions and no effects of CoPP or SnPP treatment.
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Figure 2: Emphysema development. Mean linear intercept (LMI) after long term smoke exposure and protoporphyrin treatment. Smoke groups are represented by closed symbols and sham smoke groups by open symbols. * indicates a significant effect of smoke exposure (p < 0.05). There were no interactions and no effects of CoPP or SnPP treatment.

Mentions: Smoking induced emphysema after 5.5 months smoke exposure, expressed as a significant increase in mean linear intercept (Figure 2, p < 0.01). There were no effects of both protoporphyrins on the mean linear intercept.


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

Brandsma CA, Hylkema MN, van der Strate BW, Slebos DJ, Luinge MA, Geerlings M, Timens W, Postma DS, Kerstjens HA - Respir. Res. (2008)

Emphysema development. Mean linear intercept (LMI) after long term smoke exposure and protoporphyrin treatment. Smoke groups are represented by closed symbols and sham smoke groups by open symbols. * indicates a significant effect of smoke exposure (p < 0.05). There were no interactions and no effects of CoPP or SnPP treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2254411&req=5

Figure 2: Emphysema development. Mean linear intercept (LMI) after long term smoke exposure and protoporphyrin treatment. Smoke groups are represented by closed symbols and sham smoke groups by open symbols. * indicates a significant effect of smoke exposure (p < 0.05). There were no interactions and no effects of CoPP or SnPP treatment.
Mentions: Smoking induced emphysema after 5.5 months smoke exposure, expressed as a significant increase in mean linear intercept (Figure 2, p < 0.01). There were no effects of both protoporphyrins on the mean linear intercept.

Bottom Line: HO-1 modulation had no effects on smoke induced emphysema development, or the increases in neutrophils and macrophages and inflammatory cytokines.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus