BIOMAT Database Logo BIOMAT Database Logo

Hyperlipoproteinemic low-density lipoprotein receptor-deficient mice are more susceptible to sepsis than corresponding wild-type mice. 2003

Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
Departments of Surgery and Physiology, Jefferson Medical College, 1025 Walnut Street, Philadelphia, PA 19107, USA. Susan.Lanza-Jacoby@mail.tju.edu

High circulating concentrations of lipoproteins have been shown to modify the cytokine response and reduce mortality after endotoxin or live bacterial challenge. Sepsis, however, is more complex than endotoxemia, and it is not clear whether elevated plasma lipoproteins will be protective. Previous studies have shown that the low-density-lipoprotein receptor deficient (LDLR-/-) mice with increased circulating LDL are protected against the lethal effects of endotoxemia and Gram-negative infection. We evaluated whether the LDLR-/- mice would be protected against the effects of sepsis induced by cecal ligation and puncture (CLP). Mortality was greater in LDLR-/-mice than in control C57Bl/6J mice. At 120 h after inducing sepsis, 20% of the control mice survived whereas none of theLDLR-/-mice were alive. Prior to inducing sepsis, serum concentrations of amyloid A protein and lipopolysaccharide binding protein (LBP) were significantly elevated in the LDLR-/-mice in comparison to the C57Bl/6J mice. Protein expression of sCD14 was also greater in the serum from the LDLR-/-mice than the C57Bl/6J mice. The elevated serum concentrations of LBP and CD14 were not associated with increases in the levels of liver CD14 mRNA and LBP mRNA. After inducing sepsis, serum concentration of interleukin (IL)-1beta was also significantly higher in LDLR-/-mice than in the control C57Bl/6J mice. These findings indicate that the LDLR-/-mice were more susceptible to the lethal effects of sepsis induced by CLP. The LDLR-/-mice also had higher serum concentrations of baseline, acute phase response proteins, SAA and LBP, and increased production of IL-1beta in response to CLP.

UI MeSH Term Description Entries
D006951 Hyperlipoproteinemias Conditions with abnormally elevated levels of LIPOPROTEINS in the blood. They may be inherited, acquired, primary, or secondary. Hyperlipoproteinemias are classified according to the pattern of lipoproteins on electrophoresis or ultracentrifugation. Hyperlipoproteinemia
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011973 Receptors, LDL Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking. LDL Receptors,Lipoprotein LDL Receptors,Receptors, Low Density Lipoprotein,LDL Receptor,LDL Receptors, Lipoprotein,Low Density Lipoprotein Receptor,Low Density Lipoprotein Receptors,Receptors, Lipoprotein, LDL,Receptor, LDL,Receptors, Lipoprotein LDL
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D004198 Disease Susceptibility A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. Diathesis,Susceptibility, Disease,Diatheses,Disease Susceptibilities,Susceptibilities, Disease
D000208 Acute Disease Disease having a short and relatively severe course. Acute Diseases,Disease, Acute,Diseases, Acute

Related Publications

Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
Interleukin-1 receptor type I gene-deficient mice are less susceptible to Staphylococcus epidermidis biomaterial-associated infection than are wild-type mice.
December 2000, Infection and immunity,
Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
In vivo glycated low-density lipoprotein is not more susceptible to oxidation than nonglycated low-density lipoprotein in type 1 diabetes.
August 2004, Metabolism: clinical and experimental,
Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
DNA-repair-deficient Rad54/Rad54B mice are more sensitive to clastogens than wild-type mice.
December 2008, Toxicology letters,
Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
High density lipoprotein metabolism in low density lipoprotein receptor-deficient mice.
September 2014, Journal of lipid research,
Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
Metallothionein-null mice are more susceptible than wild-type mice to chronic CdCl(2)-induced bone injury.
July 2000, Toxicological sciences : an official journal of the Society of Toxicology,
Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
Polymeric IgR knockout mice are more susceptible to mycobacterial infections in the respiratory tract than wild-type mice.
May 2006, International immunology,
Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
Obesity causes very low density lipoprotein clearance defects in low-density lipoprotein receptor-deficient mice.
November 2007, The Journal of nutritional biochemistry,
Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
Autophagy-deficient mice are more susceptible to engrafted leukemogenesis.
July 2019, Blood cells, molecules & diseases,
Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
COX-2-deficient mice are less prone to MPTP-neurotoxicity than wild-type mice.
October 2003, Neuroreport,
Susan Lanza-Jacoby, and Sheldon Miller, and Shushan Jacob, and Didier Heumann, and Alexander G Minchenko, and John T Flynn
The lupus susceptibility locus Sle3 is not sufficient to accelerate atherosclerosis in lupus-susceptible low density lipoprotein receptor-deficient mice.
January 2010, Lupus,
Copied contents to your clipboard!