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

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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.