Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Respir Physiol Neurobiol. 2011 Sep 15;178(2):304-14. doi: 10.1016/j.resp.2011.06.029. Epub 2011 Jul 6.
We tested the hypothesis that bone marrow-derived mononuclear cells (BMDMCs) at an early phase of cecal ligation and puncture (CLP)-induced sepsis may have lasting effects on: (1) lung mechanics and histology, (2) the structural remodelling of lung parenchyma, (3) lung, kidney, and liver cell apoptosis, and (4) pro- and anti-inflammatory cytokines and growth factors. At day 1, BMDMC significantly reduced mortality, as well as caspase-3, interleukin (IL)-6 and IL-1β, vascular endothelial growth factor, platelet-derived growth factor, hepatocyte growth factor, and transforming growth factor-β, but increased IL-10 mRNA expression in lung tissue in septic mice contributing to endothelium and epithelium alveolar repair and improvement of lung mechanics. BMDMC also prevented the increase of apoptotic cells in lung, liver, and kidney. At day 7, these early functional and morphological effects were preserved or further improved. In conclusion, in the present model of sepsis, the beneficial effects of early administration of BMDMCs on lung and distal organs were preserved, possibly by paracrine mechanisms.
我们检验了这样一个假说，即在盲肠结扎穿孔（CLP）诱导的脓毒症早期，骨髓来源的单核细胞（BMDMC）可能对以下方面产生持久影响：（1）肺力学和组织学，（2）肺实质的结构重塑，（3）肺、肾和肝细胞凋亡，以及（4）促炎和抗炎细胞因子和生长因子。在第 1 天，BMDMC 显著降低了脓毒症小鼠的死亡率，以及 caspase-3、白细胞介素（IL）-6 和 IL-1β、血管内皮生长因子、血小板衍生生长因子、肝细胞生长因子和转化生长因子-β的水平，但增加了肺组织中 IL-10mRNA 的表达，有助于肺泡上皮和内皮的修复，改善肺力学。BMDMC 还可防止肺、肝和肾中凋亡细胞的增加。在第 7 天，这些早期的功能和形态学效应得以维持或进一步改善。总之，在本脓毒症模型中，BMDMC 早期给药对肺和远端器官的有益作用得以保留，可能是通过旁分泌机制。
