Adenovirus-mediated transfer of a gene encoding acyloxyacyl hydrolase (AOAH) into mice increases tissue and plasma AOAH activity.

Infection and Immunity
M G CoulthardR S Meidell

Abstract

Although the host response to gram-negative bacterial infection follows largely from the interactions of bacterial lipopolysaccharides (LPS or endotoxin) with host cells, little information is available concerning the mechanisms by which the host eliminates or detoxifies LPS. Acyloxyacyl hydrolase (AOAH) is an enzyme, found in phagocytic cells, that catalyzes the enzymatic deacylation of the lipid A moiety of LPS. Enzymatically deacylated LPS is much less potent than LPS at inducing responses in human cells, and it can antagonize the ability of LPS to activate human macrophages, neutrophils, and endothelial cells. Despite these observations, the physiologic role of LPS deacylation remains undefined. To investigate the ability of AOAH to carry out LPS deacylation in vivo, we produced a recombinant adenovirus carrying a gene encoding (AOAH) (Ad.CMV-AOAH) and employed this vector to elicit transient overexpression of AOAH in mice. Mice infected with Ad.CMV-AOAH expressed high levels of the enzyme in plasma, liver, spleen, and kidney. Although adenovirus-induced hepatitis reduced hepatic uptake of intravenously injected [3H]LPS, animals expressing the transgene deacylated a larger fraction of the [3H]LPS taken up by their livers th...Continue Reading

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Citations

Oct 23, 1997·Nature Biotechnology·A W VarleyR S Munford
Feb 27, 2007·The Journal of Biological Chemistry·Baomei ShaoRobert S Munford
Nov 30, 2006·The Journal of Gene Medicine·Gang CaiQian Shen
Aug 19, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhili YaoLatha P Ganesan
Nov 10, 2017·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Wenbin YangDavid J Klumpp
Aug 8, 2017·International Reviews of Immunology·Tola A FarajClett Erridge
May 15, 2001·Toxicology and Applied Pharmacology·J CowanR S Munford

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