Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection
Lipoproteins are able to neutralize bacterial lipopolysaccharide (LPS) and thereby inhibit the proinflammatory cytokine response. In a previous study, we demonstrated that hypercholesterolemic low density lipoprotein receptor knock-out (LDLr–/–) mice are protected against lethal endotoxemia and gram...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
1999-04-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520321477 |
| _version_ | 1818827625000337408 |
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| author | Natasja de Bont Mihai G. Netea Pierre N.M. Demacker Ineke Verschueren Bart Jan Kullberg Ko Willems van Dijk Jos W.M. van der Meer Anton F.H. Stalenhoef |
| author_facet | Natasja de Bont Mihai G. Netea Pierre N.M. Demacker Ineke Verschueren Bart Jan Kullberg Ko Willems van Dijk Jos W.M. van der Meer Anton F.H. Stalenhoef |
| author_sort | Natasja de Bont |
| collection | DOAJ |
| description | Lipoproteins are able to neutralize bacterial lipopolysaccharide (LPS) and thereby inhibit the proinflammatory cytokine response. In a previous study, we demonstrated that hypercholesterolemic low density lipoprotein receptor knock-out (LDLr–/–) mice are protected against lethal endotoxemia and gram-negative infection. In the present study we investigated the susceptibility of apolipoprotein E knock-out mice (apoE–/–) to LPS and to Klebsiella pneumoniae. These mice have increased plasma lipoprotein concentrations in the very low density lipoprotein (VLDL)-sized fraction. Despite 8-fold higher plasma cholesterol levels compared to controls, and in contrast to LDLr–/– mice, apoE–/– mice were significantly more susceptible to endotoxemia and to K. pneumoniae infection. Circulating TNFα concentrations after intravenously injected LPS were 4- to 5-fold higher in apoE–/– mice, whereas IL-1α, IL-1β, and IL-6 did not differ. This TNF response was not due to an increased cytokine production capacity of cells from apoE–/– mice, as ex vivo cytokine production in response to LPS did not differ between apoE–/– and control mice. The LPS-neutralizing capacity of apoE–/– plasma was significantly less than that of controls. Most likely, the absence of apoE itself in the knock-out mice explains the failure to neutralize LPS, despite the very high cholesterol concentrations.—de Bont, N., M. G. Netea, P. N. M. Demacker, I. Verschueren, B. J. Kullberg, K. W. van Dijk, J. W. M. van der Meer, and A. F. H. Stalenhoef. Apolipoprotein E knockout-mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection. J. Lipid Res. 1999. 40: 680–685. |
| first_indexed | 2024-12-19T00:46:31Z |
| format | Article |
| id | doaj.art-aeffabb15ae14d129be70d7ff0ba8a98 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-19T00:46:31Z |
| publishDate | 1999-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-aeffabb15ae14d129be70d7ff0ba8a982022-12-21T20:44:15ZengElsevierJournal of Lipid Research0022-22751999-04-01404680685Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infectionNatasja de Bont0Mihai G. Netea1Pierre N.M. Demacker2Ineke Verschueren3Bart Jan Kullberg4Ko Willems van Dijk5Jos W.M. van der Meer6Anton F.H. Stalenhoef7Division of General Internal Medicine, Department of Medicine, University Hospital Nijmegen, 6500 HB Nijmegen, The NetherlandsDivision of General Internal Medicine, Department of Medicine, University Hospital Nijmegen, 6500 HB Nijmegen, The NetherlandsDivision of General Internal Medicine, Department of Medicine, University Hospital Nijmegen, 6500 HB Nijmegen, The NetherlandsDivision of General Internal Medicine, Department of Medicine, University Hospital Nijmegen, 6500 HB Nijmegen, The NetherlandsDivision of General Internal Medicine, Department of Medicine, University Hospital Nijmegen, 6500 HB Nijmegen, The NetherlandsDepartment of Human Genetics, Leiden University Medical Centre, Leiden, The NetherlandsDivision of General Internal Medicine, Department of Medicine, University Hospital Nijmegen, 6500 HB Nijmegen, The NetherlandsTo whom correspondence should be addressed.; Division of General Internal Medicine, Department of Medicine, University Hospital Nijmegen, 6500 HB Nijmegen, The NetherlandsLipoproteins are able to neutralize bacterial lipopolysaccharide (LPS) and thereby inhibit the proinflammatory cytokine response. In a previous study, we demonstrated that hypercholesterolemic low density lipoprotein receptor knock-out (LDLr–/–) mice are protected against lethal endotoxemia and gram-negative infection. In the present study we investigated the susceptibility of apolipoprotein E knock-out mice (apoE–/–) to LPS and to Klebsiella pneumoniae. These mice have increased plasma lipoprotein concentrations in the very low density lipoprotein (VLDL)-sized fraction. Despite 8-fold higher plasma cholesterol levels compared to controls, and in contrast to LDLr–/– mice, apoE–/– mice were significantly more susceptible to endotoxemia and to K. pneumoniae infection. Circulating TNFα concentrations after intravenously injected LPS were 4- to 5-fold higher in apoE–/– mice, whereas IL-1α, IL-1β, and IL-6 did not differ. This TNF response was not due to an increased cytokine production capacity of cells from apoE–/– mice, as ex vivo cytokine production in response to LPS did not differ between apoE–/– and control mice. The LPS-neutralizing capacity of apoE–/– plasma was significantly less than that of controls. Most likely, the absence of apoE itself in the knock-out mice explains the failure to neutralize LPS, despite the very high cholesterol concentrations.—de Bont, N., M. G. Netea, P. N. M. Demacker, I. Verschueren, B. J. Kullberg, K. W. van Dijk, J. W. M. van der Meer, and A. F. H. Stalenhoef. Apolipoprotein E knockout-mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection. J. Lipid Res. 1999. 40: 680–685.http://www.sciencedirect.com/science/article/pii/S0022227520321477lipopolysaccharidetumor necrosis factorapolipoprotein Ehypercholesterolemianeutralization |
| spellingShingle | Natasja de Bont Mihai G. Netea Pierre N.M. Demacker Ineke Verschueren Bart Jan Kullberg Ko Willems van Dijk Jos W.M. van der Meer Anton F.H. Stalenhoef Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection Journal of Lipid Research lipopolysaccharide tumor necrosis factor apolipoprotein E hypercholesterolemia neutralization |
| title | Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection |
| title_full | Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection |
| title_fullStr | Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection |
| title_full_unstemmed | Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection |
| title_short | Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection |
| title_sort | apolipoprotein e knock out mice are highly susceptible to endotoxemia and klebsiella pneumoniae infection |
| topic | lipopolysaccharide tumor necrosis factor apolipoprotein E hypercholesterolemia neutralization |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520321477 |
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