Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Danone Nutricia Research, Utrecht, The Netherlands.
Am J Physiol Lung Cell Mol Physiol. 2022 Sep 1;323(3):L266-L280. doi: 10.1152/ajplung.00486.2021. Epub 2022 Jun 14.
Chronic obstructive pulmonary disease (COPD) is often associated with intestinal comorbidities. In this study, changes in intestinal homeostasis and immunity in a cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced COPD model were investigated. Mice were exposed to cigarette smoke or air for 72 days, except , , and on which the mice were treated with saline or LPS via intratracheal instillation. Cigarette smoke exposure increased the airway inflammatory cell numbers, mucus production, and different inflammatory mediators, including C-reactive protein (CRP) and keratinocyte-derived chemokine (KC), in bronchoalveolar lavage (BAL) fluid and serum. LPS did not further impact airway inflammatory cell numbers or mucus production but decreased inflammatory mediator levels in BAL fluid. T helper (Th) 1 cells were enhanced in the spleen after cigarette smoke exposure; however, in combination with LPS, cigarette exposure caused an increase in Th1 and Th2 cells. Histomorphological changes were observed in the proximal small intestine after cigarette smoke exposure, and addition of LPS had no effect. Cigarette smoke activated the intestinal immune network for IgA production in the distal small intestine that was associated with increased fecal sIgA levels and enlargement of Peyer's patches. Cigarette smoke plus LPS decreased fecal sIgA levels and the size of Peyer's patches. In conclusion, cigarette smoke with or without LPS affects intestinal health as observed by changes in intestinal histomorphology and immune network for IgA production. Elevated systemic mediators might play a role in the lung-gut cross talk. These findings contribute to a better understanding of intestinal disorders related to COPD.
慢性阻塞性肺疾病（COPD）常伴有肠道合并症。在这项研究中，研究了香烟烟雾（CS）和脂多糖（LPS）诱导的 COPD 模型中肠道平衡和免疫的变化。将小鼠暴露于香烟烟雾或空气中 72 天，除了 、 、 天之外，这些天通过气管内滴注用生理盐水或 LPS 处理小鼠。香烟烟雾暴露增加了气道炎症细胞数量、粘液产生以及不同的炎症介质，包括 C 反应蛋白（CRP）和角质细胞衍生的趋化因子（KC），在支气管肺泡灌洗液（BAL）和血清中。LPS 没有进一步影响气道炎症细胞数量或粘液产生，但降低了 BAL 液中的炎症介质水平。香烟烟雾暴露后脾脏中 Th1 细胞增加；然而，与 LPS 联合使用时，香烟暴露导致 Th1 和 Th2 细胞增加。香烟烟雾暴露后观察到近端小肠的组织形态学变化，而 LPS 的添加没有影响。香烟烟雾激活了远端小肠的 IgA 产生的肠道免疫网络，这与粪便 sIgA 水平升高和派尔氏斑增大有关。香烟烟雾加 LPS 降低了粪便 sIgA 水平和派尔氏斑的大小。总之，香烟烟雾加或不加 LPS 都会影响肠道健康，如肠道组织形态学和 IgA 产生的肠道免疫网络的变化。升高的系统介质可能在肺-肠相互作用中发挥作用。这些发现有助于更好地理解与 COPD 相关的肠道紊乱。
