The role of splenic macrophages in plasma tumor necrosis factor levels in endotoxemia

We investigated the function of splenic macrophages (M phi s) with respect to changes in plasma tumor necrosis factor (TNF) in lethally endotoxemic rats treated with gadolinium chloride (GdCl3), which blocks the phagocytosis of large liver M phi s. We also carried out an immunohistochemical study to investigate the change of populations of liver and splenic M phi s under the condition of dysfunction of liver M phi s with or without splenectomy. Twenty-four-hour survival rates were 100% in the GdCl3-treated group (n = 6) and 0% in the nontreated group (n = 6). These rates did not change with splenectomy. Immunohistochemical examination with the primary monoclonal antibodies ED1, ED2 and ED3 revealed that large liver M phi s were eliminated after GdCl3 injection, and that this was not related to splenectomy. The splenic M phi s were not affected by GdCl3 treatment. Plasma TNF levels did not differ between the GdCl3-treated and the nontreated groups, irrespective of whether splenectomy was performed. It was suggested that plasma TNF levels are not affected by the splenic M phi s and that they do not compensate for dysfunction of liver M phi s after GdCl3 treatment.