Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats.
Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats.
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DOI：
10.1186/s13054-018-2164-0
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发表时间：
2018-10-05
期刊：
影响因子：
--
通讯作者：
Rocco PRM
中科院分区：
文献类型：
--
作者：
Samary CS;Ramos AB;Maia LA;Rocha NN;Santos CL;Magalhães RF;Clevelario AL;Pimentel-Coelho PM;Mendez-Otero R;Cruz FF;Capelozzi VL;Ferreira TPT;Koch T;de Abreu MG;Dos Santos CC;Pelosi P;Silva PL;Rocco PRM
缺血性中风会引起脑部炎症，我们推测这可能会导致肺损伤。一些研究集中于中风引起的免疫抑制和肺部感染；然而，中风可能引发肺部炎症的可能性被忽视了。我们假设，即使是局灶性缺血性卒中也可能导致急性全身和肺部炎症，从而改变呼吸参数、肺组织完整性和肺泡巨噬细胞行为。48只Wistar大鼠随机分为缺血性卒中组(卒中组)和假手术组(Sham组)。观察24小时肺功能、组织学、肺、脑、支气管肺泡灌洗液(BALF)和循环血浆中的炎症反应。体外，未受刺激的幼年大鼠肺泡巨噬细胞暴露于Sham或卒中动物的血清或BALF中，以阐明肺泡巨噬细胞吞噬能力改变的可能机制。分离假手术组和卒中组大鼠肺泡巨噬细胞、上皮细胞和内皮细胞，检测白细胞介素6和肿瘤坏死因子α的表达。缺血性卒中后24小时，潮气量、呼气时间和平均吸气流量增加。与Sham动物相比，自主呼吸时的呼吸频率和占空比降低，但不影响机械通气时的肺力学性能。中风动物的肺显示出明显的弥漫性肺泡损伤、肺水肿和炎症标志物增加的证据。这与超微结构损伤增加有关，表现为对2型肺泡细胞和内皮细胞的损伤、细胞浸润和基底膜增厚。在肺、脑、血浆(肿瘤坏死因子-α和IL-6)和肺泡灌洗液(肿瘤坏死因子-α)中记录促炎介质的蛋白水平。巨噬细胞的吞噬能力明显降低。从幼稚大鼠分离的未受刺激的巨噬细胞仅在暴露于中风大鼠的血清后上调肿瘤坏死因子-α和IL-6的表达。暴露于中风或假手术动物的肺泡灌洗液不会改变肺泡巨噬细胞的行为，也不会改变肿瘤坏死因子-α和白介素6的基因表达。卒中大鼠巨噬细胞和血管内皮细胞IL-6表达增加。在大鼠中，局灶性缺血性卒中与脑-肺串扰有关，导致肺损伤和炎症增加，以及肺泡巨噬细胞吞噬能力降低，这似乎是由全身炎症促进的。本文的在线版本(10.1186/s13054-0182164-0)包含补充材料，可供授权用户使用。
Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior. Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naïve rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-α and IL-6) and in BALF (TNF-α). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naïve rats only upregulated expression of TNF-α and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-α and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals. In rats, focal ischemic stroke is associated with brain–lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation. The online version of this article (10.1186/s13054-018-2164-0) contains supplementary material, which is available to authorized users.
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影响因子：
2.3
作者：
Chao, Monica C. M.;Garcia, Cristiane S. N. B.;Rocco, Patricia R. M.
通讯作者：
Rocco, Patricia R. M.
影响因子：
8.3
作者：
Engel, Odilo;Akyuez, Levent;Meisel, Andreas
通讯作者：
Meisel, Andreas
影响因子：
168.9
作者：
Kalra, Lalit;Irshad, Saddif;Rebollo-Mesa, Irene
通讯作者：
Rebollo-Mesa, Irene
影响因子：
1.9
作者：
Bar-Joseph, Gad;Guilburd, Yoav;Guilburd, Joseph N.
通讯作者：
Guilburd, Joseph N.
影响因子：
2.9
作者：
dos Santos, Andreia de Vasconcelos;Reis, Juliana da Costa;Mendez-Otero, Rosalia
通讯作者：
Mendez-Otero, Rosalia