Apolipoprotein E-deficient mice have an impaired immune response to Klebsiella pneumoniae

Authors: de Bont N.¹; Netea M.G.¹; Demacker P.N.M.¹; Kullberg B.J.¹; van der Meer J.W.M.¹; Stalenhoef A.F.H.^{1, *}

Source: European Journal of Clinical Investigation, Volume 30, Number 9, September 2000 , pp. 818-822(05)

Publisher: Wiley-Blackwell

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- (TNF-) 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- 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: Apo E deficient mice; Klebisiella pneumoniae; lipoproteins; hypercholesterolemia; survival; TNF

Language: English

Document Type: Research article

Affiliations: 1: Academic Medical Center Nijmegen, the Netherlands *

Publication date: 2000-09-01

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• In this Subject: Public Health
• By this author: de Bont N. ;  Netea M.G. ;  Demacker P.N.M. ;  Kullberg B.J. ;  van der Meer J.W.M. ;  Stalenhoef A.F.H.

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