Bacterial translocation and lipopolysaccharide-induced mortality in genetically macrophage-deficient op/op mice.
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.
Feltis
B A
BA
Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis 55455, USA.
Jechorek
R P
RP
Erlandsen
S L
SL
Wells
C L
CL
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004926:Escherichia coli / Q000254:growth & development / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000378:metabolism / Q000401:mortality* / Q000503:physiopathology; D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D012772:Shock, Septic / Q000378:metabolism / Q000401:mortality* / Q000503:physiopathology
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor