Antibody Blocks Inflammation, Protects Mice From Hardened Arteries and Liver Disease

Source: University of California -San Diego

Summary: Researchers have discovered that they can block inflammation in mice with a naturally occurring antibody that binds oxidized phospholipids (OxPL), molecules on cell surfaces that get modified by inflammation.

Some phospholipids, the molecules that make up cell membranes are prone to modification by reactive oxygen species, forming OxPL. This event is particularly common in inflammatory conditions such as atherosclerosis, in which artery-blocking plaques form. Prior to this study, researchers were unable to control phospholipid oxidation in a way that would allow them to study its role in inflammation and atherosclerosis. Researchers from the University of California – San Diego have discovered that they can block inflammation in mice with a naturally occurring antibody that binds oxidized phospholipids (OxPL), molecules on cell surfaces that get modified by inflammation. The results suggest a new approach for preventing or reversing a number of inflammatory diseases. The study findings were published in the journal Nature.

E06 Antibody

The aorta of a mouse model of atherosclerosis on a high-fat diet for 12 months (top) has significantly more plaques (bright red) than the aorta of the same type of mouse that also produces the anti-inflammatory E06 antibody (bottom). Credit: UC San Diego Health

The research team engineered mice with two special attributes – 1) they have a gene mutation that makes them a good model for atherosclerosis and 2) they generate a piece of an antibody called E06 that’s just enough to bind OxPL and prevent their ability to cause inflammation in immune cells, but not enough to cause inflammation on its own. They fed the mice a high-fat diet. Compared to control mice, the mice with E06 antibodies had 28-57% less atherosclerosis, even after 1 year and despite having high levels of cholesterol. The antibody also decreased aortic valve calcification (hardening and narrowing of the aortic valves), hepatic steatosis (fatty liver disease) and liver inflammation. E06 antibody-producing mice had 32% less serum amyloid A, a marker of systemic inflammation.

Prof. Joseph Witztum said, “We showed for the first time that OxPL are truly pro-inflammatory and pro-atherogenic and, moreover, that they can be counteracted by E06 antibody.”

More Information: Xuchu Que et al, Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice, Nature (2018). DOI: 10.1038/s41586-018-0198-8 

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