Heme oxygenase-1 prevents smoke induced B-cell infiltrates: a role for regulatory T cells?
Heme oxygenase-1 prevents smoke induced B-cell infiltrates: a role for regulatory T cells?
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DOI：
10.1186/1465-9921-9-17
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发表时间：
2008-02-06
影响因子：
5.8
通讯作者：
Kerstjens, Huib A. M.
中科院分区：
文献类型：
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作者：
Brandsma, Corry-Anke;Hylkema, Machteld N.;Kerstjens, Huib A. M.
背景：吸烟是慢性阻塞性肺病（COPD）发生的最重要原因。由于并非所有吸烟者都会患慢性阻塞性肺病，因此很明显，疾病的发生一定涉及其他因素。我们假设血红素加氧酶-1 (HO-1)（一种针对氧化应激和炎症的保护酶）在 COPD 中没有充分上调。在吸烟小鼠模型中测试了 HO-1 调节对香烟烟雾诱发的炎症和肺气肿的影响。方法：将小鼠暴露或假暴露于香烟烟雾中 20 周。在此期间注射钴原卟啉或锡原卟啉分别诱导或抑制HO-1活性。随后，分析肺气肿的发展、炎症细胞和细胞因子的水平以及肺组织中 B 细胞浸润的存在。结果：烟雾暴露诱发肺气肿，并增加炎症细胞和 B 细胞浸润的数量以及肺组织中炎症细胞因子的水平。 HO-1 调节对烟雾诱发的肺气肿发展或中性粒细胞、巨噬细胞和炎症细胞因子的增加没有影响。有趣的是，HO-1诱导阻止了烟雾诱导的B细胞浸润的发展，并增加了肺部CD4(+) CD25(+) T细胞和Foxp3阳性细胞的水平。此外，CD4(+) CD25(+) T细胞与肺组织中Foxp3阳性细胞的数量呈正相关，表明这些细胞是调节性T细胞。结论：这些结果支持HO-1表达影响调节性T细胞的概念，并表明该机制参与抑制烟雾诱导的B细胞浸润。现在应该将这种相互作用转化为人类慢性阻塞性肺病。
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.