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BACTERIAL TRANSLOCATION AND LIPOPOLYSACCHARIDE-INDUCED MORTALITY IN GENETICALLY MACROPHAGE-DEFICIENT op/op MICE

Feltis, Brad A.*; Jechorek, Robert P.*; Erlandsen, Stanley L.‡; Wells, Carol L.*‡

*Departments of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota 55455

‡Departments of Surgery, University of Minnesota, Minneapolis, Minnesota 55455

§Cell Biology & Neuroanatomy, University of Minnesota, Minneapolis, Minnesota 55455

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Abstract

Genetically macrophage-deficient op/op mice have a total absence of macrophage colony-stimulating factor (also known as colony-stimulating factor 1 or CSF−1), and therefore an absence of a population of macrophages dependent on CSF−1. op/op mice also have profound secondary deficiencies in certain cytokines secreted by this macrophage population, such as tumor necrosis factor, interleukin−1, and granulocyte colony-stimulating factor. In the present study, op/op mice were used to clarify the role of the macrophage in two clinical processes: (a) bacterial translocation in response to antibiotic-induced intestinal overgrowth, and (b) endotoxin-induced bacterial translocation, morbidity, and mortality. The results were unexpected, in that bacterial translocation and endotoxin-induced morbidity and mortality were similar in op/op mice and their functionally normal littermates. These data indicated either that a specific macrophage population and its cytokines (including tumor necrosis factor and interleukin 1) might not play pivotal roles in the pathogenesis of bacterial translocation and endotoxin-induced septic shock, or alternatively, as yet unknown redundancies in vivo might compensate for the genetic deficiencies associated with the op/op mutation.