title: Apolipoprotein E-deficient mice have an impaired immune response to Klebsiella pneumoniae.
abstract: BACKGROUND
  All lipoproteins are able to bind to bacterial lipopolysaccharide (LPS), thereby neutralizing its deleterious effects. However, we demonstrated, recently, that in the absence of apolipoprotein E (apoE), eight-fold increased very-low-density lipoprotein levels were not sufficient to protect apoE-deficient (apoE-/-) mice against LPS. During a live Gram-negative infection, mechanisms other than LPS-neutralization may play a role in the pathogenesis of the disease. In the present study we further examined the role of apoE in Gram-negative sepsis.
  
  
  METHODS
  Survival, bacterial outgrowth in liver, spleen, kidneys and blood, and tumour necrosis factor-alpha (TNF-alpha) production were measured in apoE-/- mice and control C57BL/6J mice, after an intravenous infection with Klebsiella pneumoniae.
  
  
  RESULTS
  Mice that lack apoE showed higher mortality in response to K. pneumoniae than control mice (90% vs. 23% respectively after 2 weeks). ApoE-/- mice had 10-100 times more outgrowth of the bacteria in their organs than controls. Furthermore, circulating TNF-alpha concentrations 90 min after a challenge, were almost twice as high in the apoE-/- mice compared to controls (13.0 +/- 2.9 ng mL-1 vs. 7.6 +/- 3.8 ng mL-1). When apoE-/- and control mice were rendered neutropenic, the discrepancy in survival and outgrowth of K. pneumoniae disappeared.
  
  
  CONCLUSIONS
  The apoE-/- mice were more susceptible than control C57BL/6 mice to a K. pneumoniae infection. The absence of apoE may render these mice more susceptible, since this protein is of importance in the detoxification of lipopolysaccharide of Gram-negative bacteria. On the other hand, the phagocytic capacity of granulocytes seems to be decreased in apoE-/- mice, resulting in increased outgrowth and mortality.
authors.affiliation: Academic Medical Center Nijmegen, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: de Bont
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: P N
authors.initials: PN
authors.lastname: Demacker
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
authors.forename: A F
authors.initials: AF
authors.lastname: Stalenhoef
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D007109:Immunity; D007710:Klebsiella Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology* / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009503:Neutropenia / Q000382:microbiology; D010446:Peptide Fragments / Q000172:deficiency / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D010446:Peptide Fragments; D014280:Triglycerides; C117630:apolipoprotein E (141-155); D002784:Cholesterol