Recent studies from this laboratory have shown that experimental injury causes a depression of the ability of hepatic macrophage complement receptors to bind erythrocytes coated with antibodies and complement. It was also shown that the depression of complement receptor function in uninjured animals was associated with increased susceptibility to infection. These findings suggest that hepatic macrophage receptor function may play an important role in mediating the depression of host defense associated with injury.
The aims of this proposal are: (1) to determine hepatic macrophage Fc receptor function. Fc receptor function will be studied because both complement and antibodies are important for the clearance and phagocytosis of bacteria. Fc receptor clearance function will be determined from the clearance of aggregated IgG and Fc receptor phagocytic function will be determined using electron microscopy. The effect of injury on hepatic Fc receptor function and the effect of Fc receptor depression on host defense will be determine, (2) to study the mechanism of the depression of hepatic complement and Fc receptor clearance function. Receptor function will be depressed by the injection of particulates. The role of the depletion of these receptors from the macrophage surface will be determined, (3) to study the mechanism of the increased susceptibility to infection associated with depressed hepatic complement and Fc receptor function. The importance of the composition of the particulate material used to depress receptor function and the role of depressed bacterial clearance, bacterial phagocytosis and bacterial killing will be determined. Another aspect of this study is to determine the degree to which the evaluation of receptor function gives an indication of host defense status. The long-range objective of this study is to elucidate the mechanism of impaired host defense in severely injured patients and thereby to provide a basis for improved diagnosis and treatment of these patients. This multidisciplinary study involves the areas of physiology, immunology, biochemistry, bacteriology, and histology represents a new approach to the mechanism of impaired host defense in severely injured patients.
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