CD4+ T lymphocytes mediate acute pulmonary ischemia-reperfusion injury.
CD4+ T lymphocytes mediate acute pulmonary ischemia-reperfusion injury.
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DOI：
10.1016/j.jtcvs.2008.10.044
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发表时间：
2009-03
影响因子：
6
通讯作者：
Laubach, Victor E.
中科院分区：
文献类型：
--
作者：
Yang, Zequan;Sharma, Ashish K.;Linden, Joel;Kron, Irving L.;Laubach, Victor E.
肺缺血后再灌注触发促炎反应，刺激有害的中性粒细胞趋化性。我们假设T淋巴细胞在再灌注过程中被募集和激活，并介导随后的嗜酸性粒细胞诱导的肺缺血再灌注损伤（IRI）。采用肺IRI的体内小鼠模型。将C57 BL/6小鼠分配到假手术组（左胸廓切开术）或7个研究组，所述研究组经历1小时左肺门闭塞，随后1-24小时再灌注。在体内再灌注后，用缓冲液离体灌注肺，由此评估肺功能。分别通过Evans蓝染料渗漏、湿/干重比、髓过氧化物酶和ELISA评估肺血管通透性、水肿、中性粒细胞蓄积和细胞因子/趋化因子（TNF-α、IL-17、CCL 3和CXCL 1）产生。初步研究表明，2小时再灌注比1小时或24小时再灌注导致更大的肺功能障碍。因此，2小时再灌注期用于剩余的实验。中性粒细胞或CD 4 + T细胞的抗体耗尽后，发生了对IR诱导的肺功能障碍和损伤的相当且显著的保护，但CD 8 + T细胞未发生（相对于IgG对照，p<0.05）。肺IRI与中性粒细胞浸润成正比，而与T细胞浸润无关。此外，肺中性粒细胞浸润和CXCL 1（KC）的产生显着减少CD 4 + T细胞耗竭，但反之亦然。CD 4 + T淋巴细胞和中性粒细胞在再灌注过程中积累，并依次导致肺IRI。这些数据表明，中性粒细胞介导IRI;然而，CD 4 + T细胞在刺激IRI期间趋化因子产生和中性粒细胞趋化性中起关键作用。
Post-ischemic reperfusion of the lung triggers pro-inflammatory responses that stimulate injurious neutrophil chemotaxis. We hypothesized that T lymphocytes are recruited and activated during reperfusion and mediate subsequent neutrophil-induced lung ischemia-reperfusion injury (IRI). An in vivo mouse model of lung IRI was employed. C57BL/6 mice were assigned to either sham group (left thoracotomy) or 7 study groups which underwent one hour left hilar occlusion followed by 1-24 hours reperfusion. Following in vivo reperfusion, the lungs were perfused ex vivo with buffer whereby pulmonary function was assessed. Lung vascular permeability, edema, neutrophil accumulation and cytokine/chemokine production (TNF-α, IL-17, CCL3, and CXCL1) were assessed by Evans blue dye leak, wet/dry weight ratio, myeloperoxidase, and ELISA, respectively. A preliminary study showed that 2-hr reperfusion resulted in greater pulmonary dysfunction than 1-hr or 24-hr reperfusion. The 2-hr reperfusion period was thus used for the remaining experiments. Comparable and significant protection from IR-induced lung dysfunction and injury occurred after antibody-depletion of neutrophils or CD4+ T cells, but not CD8+ T cells (p<0.05 vs. IgG control). Lung IRI was proportional to the infiltration of neutrophils but not T cells. Moreover, pulmonary neutrophil infiltration and the production of CXCL1 (KC) were significantly diminished by CD4+ T cell depletion, but not vice versa. Both CD4+ T lymphocytes and neutrophils accumulate during reperfusion and contribute sequentially to lung IRI. The data suggest that neutrophils mediate IRI; however, CD4+ T cells play a critical role in stimulating chemokine production and neutrophil chemotaxis during IRI.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1164/rccm.2112012
发表时间：
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影响因子：
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DOI：
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发表时间：
2008-01-01
影响因子：
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作者：
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影响因子：
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