Heme oxygenase-1 attenuates acute pulmonary inflammation by decreasing the release of segmented neutrophils from the bone marrow
Heme oxygenase-1 attenuates acute pulmonary inflammation by decreasing the release of segmented neutrophils from the bone marrow
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DOI：
10.1152/ajplung.00145.2014
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发表时间：
2014-11-01
影响因子：
4.9
通讯作者：
Reutershan, Joerg
中科院分区：
文献类型：
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作者：
Konrad, Franziska M.;Braun, Stefan;Reutershan, Joerg
从循环系统和骨髓中招募多形核中性粒细胞（PMN）到炎症部位是先天免疫系统的关键机制之一。在炎症过程中，血红素加氧酶1（HO - 1）已被证明可减少PMN的迁移。尽管这些作用在各种模型中都有描述，但其潜在机制仍不清楚。近期研究揭示了HO - 1对骨髓中不同细胞的影响。我们研究了骨髓在HO - 1依赖性肺部炎症方面的特殊作用。在脂多糖（LPS）吸入的小鼠模型中，氯化钴（III）原卟啉 - IX（CoPP）刺激HO - 1导致分叶核PMN向肺泡腔的迁移减少。在CoPP组中，血管内分叶核PMN也减少，并且相应地，骨髓中成熟和未成熟PMN数量增加。锡原卟啉 - IX对该酶的抑制增加了分叶核和杆状PMN向支气管肺泡灌洗液的迁移，同时伴有PMN从骨髓释放增加以及组织炎症参数加重。未成熟PMN的氧化爆发活性明显高于成熟PMN。趋化因子基质细胞衍生因子 - 1（SDF - 1）可介导白细胞归巢到骨髓且在炎症中降低，CoPP可使其增加。当SDF - 1被特异性拮抗剂AMD3100阻断时，HO - 1激活在抑制PMN向发炎肺部的运输方面不再有效。总之，我们有证据表明HO - 1的抗炎作用主要是通过抑制分叶核PMN从骨髓释放来介导的，而非在肺部内的直接作用。
Recruiting polymorphonuclear neutrophil granulocytes (PMNs) from circulation and bone marrow to the site of inflammation is one of the pivotal mechanisms of the innate immune system. During inflammation, the enzyme heme oxygenase 1 (HO-1) has been shown to reduce PMN migration. Although these effects have been described in various models, underlying mechanisms remain elusive. Recent studies revealed an influence of HO-1 on different cells of the bone marrow. We investigated the particular role of the bone marrow in terms of HO-1-dependent pulmonary inflammation. In a murine model of LPS inhalation, stimulation of HO-1 by cobalt (III) protoporphyrin-IX-chloride (CoPP) resulted in reduced segmented PMN migration into the alveolar space. In the CoPP group, segmented PMNs were also decreased intravascularly, and concordantly, mature and immature PMN populations were higher in the bone marrow. Inhibition of the enzyme by tin protoporphyrin-IX increased segmented and banded PMN migration into the bronchoalveolar lavage fluid with enhanced PMN release from the bone marrow and aggravated parameters of tissue inflammation. Oxidative burst activity was significantly higher in immature compared with mature PMNs. The chemokine stromal-derived factor-1 (SDF-1), which mediates homing of leukocytes into the bone marrow and is decreased in inflammation, was increased by CoPP. When SDF-1 was blocked by the specific antagonist AMD3100, HO-1 activation was no longer effective in curbing PMN trafficking to the inflamed lungs. In conclusion, we show evidence that the anti-inflammatory effects of HO-1 are largely mediated by inhibiting the release of segmented PMNs from the bone marrow rather than direct effects within the lung.