Role of Kupffer Cells in Lung Injury in Rats Administered Endotoxin11

The purpose of this study was to investigate the regulation of lung macrophages (Μϕs) by Kupffer cells (KCs) in lung injury caused by endotoxemia. Phenotypic differences in tissue Μϕs were also investigated. Μϕs were isolated from gadolinium chloride (GdCl3)- or saline-treated rats 2 h after saline or lipopolysaccharide (LPS) administration. Furthermore, rats were given GdCl3 24 h prior to LPS administration, and survival rate was assessed for 24 h. Moreover, lung edema was assessed 9 h after LPS injection. Expression of inflammatory mediators was measured in the liver and lung. KCs were divided into three subpopulations based on size and phagocytosis. The expression of TNF-α and MIP-2 was greater in the small KCs and lung Μϕs, while the expression of IL-6, IL-10, and MCP-1 was greater in the large and intermediate KCs. GdCl3 eliminated ED2-positive large KCs and did not have any effect on the lung Μϕs. The number of ED1-positive KCs increased significantly in both organs after LPS challenge and was reduced by GdCl3. The population of ED2-positive KCs did not change following LPS administration. GdCl3 completely prevented increases in lung microvascular permeability and mortality after LPS infusion. After LPS administration, expression of TNF-α and IL-6 increased rapidly and then decreased gradually in both organs. GdCl3 inhibited these increases in the liver significantly and enhanced the expression of MCP-1 and IL-10 in the lung 9 h after LPS administration. Thus, the heterogeneous response of KCs to endotoxin leads to production of certain cytokines and chemokines that affect lung function.