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Chylomicrons alter the hepatic distribution and cellular response to endotoxin in rats
Author(s) -
Harris Hobart W.,
Rockey Don C.,
Chau Phuonglan
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510270521
Subject(s) - lipopolysaccharide , tumor necrosis factor alpha , kupffer cell , stimulation , proinflammatory cytokine , nitric oxide , cytokine , medicine , chemistry , endocrinology , nitric oxide synthase , hepatocyte , liver cytology , in vitro , biology , inflammation , microbiology and biotechnology , immunology , biochemistry , liver metabolism
Chylomicrons (CM) can bind endotoxin (lipopolysaccharide [LPS]), forming CM‐LPS complexes, and protect against endotoxic shock and death in rodent models of gram‐negative sepsis. The liver appears to play a central role in this process, as demonstrated by the increased uptake of LPS by this organ. We examined the effect of CM on the uptake and cellular response to injected 125 I‐LPS by hepatocytes and hepatic nonparenchymal cells. Whereas CM increased the uptake of LPS by both hepatocytes and Kupffer cells, the increase was proportionately greater in hepatocytes than Kupffer cells. Importantly, CM‐LPS complexes inhibited inducible nitric oxide synthase (iNOS) mRNA expression and NO production in Kupffer cells and endothelial cells, reducing mRNA levels by 45% to 50% as compared with LPS alone. CM‐bound LPS also reduced NO production by hepatocytes in response to cytokine stimulation. Lastly, CM‐LPS complexes yielded a concentration‐dependent inhibition of LPS‐induced tumor necrosis factor α (TNF‐α) production by Kupffer cells in vitro . These data indicate that the mechanism by which CM protect against endotoxicity may involve an increased uptake of LPS by hepatocytes. Moreover, uptake of CM‐bound LPS by liver cells attenuates the capacity of these cells to respond to proinflammatory stimulation. These results highlight important anti‐inflammatory properties of CM.