Investigation of heterogeneity of tissue macrophages and inflammatory immune response during infection.

本实验采用大鼠腹膜炎和内毒素快速输注两种不同的炎症模型，研究枯否细胞（KCs）在急性肺损伤中的作用。此外，还研究了KCs和组织巨噬细胞（Mφ）的表型和功能差异。在注射LPS前24 h给予GdCl_3，观察24 h存活率。在另一组实验中，在盲肠结扎和穿孔（CLP）前24小时，给大鼠注射生理盐水或氯化钆（GdCl_3）（KC毒物）。CLP后7天评估生存率。GdCl_3完全阻止LPS推注后肺微血管通透性和死亡率的增加。另一方面，GdCl_3处理增加了肺损伤，降低了存活率。此外，从表型分析，KCs分为3个亚群的基础上的大小和吞噬功能。此外，还观察到组织Mφ对内毒素反应的功能差异。因此，KCs和组织Mφ对内毒素的异质性反应导致某些影响肺功能的细胞因子和趋化因子的产生。此外，KCs在急性肺损伤中的作用取决于炎症过程中的病理生理状态。

The role of Kupffer cells (KCs) in acute lung injury was investigated in two different inflammatory models, peritonitis and endotoxin bolus infusion models, in rats. Furthermore, phenotypic and functional differences in KCs and tissue macrophages (Mφs) were also investigated. Rats were given GdCl_3 24 hours prior to LPS administration, and survival rate was assessed for 24 hours. In another set of experiments, rats were given saline or gadolinium chloride (GdCl_3), a KC toxicant, 24 hours before cecal ligation and puncture (CLP). Survival was assessed for 7 days after CLP. GdCl_3 completely prevented increases in lung microvascular permeability and mortality after LPS bolus infusion. On the other hand, GdCl_3 treatment increased lung injury and reduced the survival rate. Furthermore, from phenotypic analysis, KCs were divided into 3 subpopulations based on size and phagocytosis. Moreover, functional differences were observed in response of tissue Mφs to endotoxin. Thus, the heterogeneous response of KCs and tissue Mφs to endotoxin leads to production of certain cytokines and chemokines that affect lung function. Furthermore, the role of KCs in acute lung injury depends on pathophysiological condition during inflammation.