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91.
Apolipoprotein E (apoE) plays important roles in lipid homeostasis, anti-inflammation, and host defense. Since tissue apoE mRNA levels have been reported to decrease during inflammatory responses, we were surprised to find that plasma apoE levels were significantly elevated during septic infections in both humans and mice. This apparent paradox was also observed during lipopolysaccharide-induced acute inflammation in mice: plasma levels of apoE increased up to 4-fold despite sharply decreased apoE gene expression in the liver, macrophages, and extrahepatic tissues. We hypothesized that apoE levels were augmented by decreased plasma clearance. Our analysis revealed that apoE associated principally with HDL in mice and that apoE was cleared from the circulation principally via LDL receptors. The acute inflammatory response decreased LDL receptor expression in the liver and significantly reduced the rate of apoE clearance. In contrast, the same inflammatory stimuli increased LDL receptor expression in macrophages. Our results define a novel acute phase mechanism that increases circulating apoE levels as apoE production decreases. Diminished hepatic LDL receptor expression may thus cooperate with elevated LDL receptor expression in macrophages to facilitate the forward transport of apoE and its associated lipids to these key defense cells. 相似文献
92.
Shams H Wizel B Lakey DL Samten B Vankayalapati R Valdivia RH Kitchens RL Griffith DE Barnes PF 《FEMS immunology and medical microbiology》2003,36(1-2):63-69
Prior reports have suggested that CD14 mediates uptake of Mycobacterium tuberculosis into porcine alveolar macrophages and human fetal microglia, but the contribution of CD14 to cell entry in human macrophages has not been studied. To address this question, we used flow cytometry to quantify uptake by human monocytes and alveolar macrophages of M. tuberculosis expressing green fluorescent protein. Neutralizing anti-CD14 antibodies did not affect bacillary uptake and the efficiency of bacillary entry was similar in THP-1 cells expressing low and high levels of CD14. However, most internalized bacteria were found in CD14+ but not in CD14- monocytes because M. tuberculosis infection upregulated CD14 expression. We conclude that: (1) CD14 does not mediate cellular entry by M. tuberculosis; (2) M. tuberculosis infection upregulates CD14 expression on mononuclear phagocytes, and this may facilitate the pathogen's capacity to modulate the immune response. 相似文献
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Testing the covarion hypothesis of molecular evolution 总被引:14,自引:8,他引:6
The covarion hypothesis of molecular evolution states that the fixation of
mutations may alter the probability that any given position will fix the
next change. Tests of this hypothesis using the divergence of real
sequences are compromised because models of rate variation among sites
(e.g., the gamma version of the one-parameter equation) predict sequence
divergence values similar to those for the covarion process. This study
therefore focuses on the extent to which the varied and unvaried codons of
two well-diverged taxa are the same, because fewer are expected by the
covarion hypothesis than by the gamma model. The data for these tests are
the protein sequences of Cu, Zn superoxide dismutase (SOD) for mammals and
plants. Simulation analyses show that the covarion hypothesis makes better
predictions about the frequencies of varied and unhit positions in common
between these two taxa than does the gamma version of the one-parameter
model. Furthermore, the analysis of SOD tertiary structure demonstrates
that mammal and plant variabilities are distributed differently on the
protein. These results support the conclusions that the variable and
invariable codons of mammal and plant SODs are different and that the
covarion model explains the evolution of this protein better than the gamma
version of the one-parameter process. Unlike other models, the covarion
hypothesis accounts for rate fluctuations among positions over time, which
is an important parameter of molecular evolution.
相似文献
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The conclusion arrived at by chemical methods, that the volatile agent produced when sulphur is applied to a heated surface is gaseous sulphur, has been subjected to biological tests in which the fungi Ery-siphe graminis and Sphaerotheca Humulind the gall mite Eriophyes ribis were employed.
The fungi were found not to be sufficiently sensitive to yield satisfactory and concordant results and strong support is given to the view that actual contact of the sulphur particle with the fungus is necessary before fungicidal action can occur.
It was shown that the agent present in air passed over heated sulphur and responsible for the death of the gall mite was not removed by filtration through a heated glass-wool plug, this observation being contrary to the view that the toxic agent is produced initially in solid form.
Filtration through a cooled glass-wool plug only removed part of the volatile agent and it was shown that the gall mite is affected by the traces of sulphur volatilised at ordinary temperatures.
The results of the experiments with the gall mite were in complete accord with those obtained in the previous chemical work.
At relatively large concentrations sulphur dioxide and hydrogen sulphide are without permanent effect upon the gall mite and these gases are therefore not responsible for the acaricidal action of sulphur. 相似文献
The fungi were found not to be sufficiently sensitive to yield satisfactory and concordant results and strong support is given to the view that actual contact of the sulphur particle with the fungus is necessary before fungicidal action can occur.
It was shown that the agent present in air passed over heated sulphur and responsible for the death of the gall mite was not removed by filtration through a heated glass-wool plug, this observation being contrary to the view that the toxic agent is produced initially in solid form.
Filtration through a cooled glass-wool plug only removed part of the volatile agent and it was shown that the gall mite is affected by the traces of sulphur volatilised at ordinary temperatures.
The results of the experiments with the gall mite were in complete accord with those obtained in the previous chemical work.
At relatively large concentrations sulphur dioxide and hydrogen sulphide are without permanent effect upon the gall mite and these gases are therefore not responsible for the acaricidal action of sulphur. 相似文献
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