Apolipoprotein E‐deficient mice have an impaired immune response to Klebsiella pneumoniae
- 1 September 2000
- journal article
- research article
- Published by Wiley in European Journal of Clinical Investigation
- Vol. 30 (9), 818-822
- https://doi.org/10.1046/j.1365-2362.2000.00715.x
Abstract
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. Survival, bacterial outgrowth in liver, spleen, kidneys and blood, and tumour necrosis factor-α (TNF-α) production were measured in apoE−/− mice and control C57BL/6J mice, after an intravenous infection with Klebsiella pneumoniae. 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-α 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. 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.Keywords
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