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Resolvin: A Potent Endo­genous Mediator of White Blood Cells

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For the immune cells that navigate the blood system, it is not where the macrophages, neutrophils, and other white blood cells start, it’s where their movements and programmed responses lead them that count. The cells must respond to immune signals, coordinate their efforts to neutralize a recognized threat, and then heed the biochemical prompts to shut down, or re­solve, the attack. Immune cells that don’t go all the way to the resolution phase re­main in persistent attack mode and, as millions of Americans can attest, their otherwise healthy tissues bear the brunt of it. But like raising one’s voice to rouse the attention of someone with plugs in his ears, scientists have wondered in recent years whether elevating proresolution molecules at sites of autoimmune attacks, such as periodontitis in the mouth and arthritis in the joints, can override and shut down the im­mune response. To find their answer, researchers have be­gun isolating and characterizing a growing number of proresolution molecules.

In the October 29 issue of the journal Nature, a team of National Institute of Dental and Craniofacial Research (NIDCR) grantees and colleagues provides the first complete stereochemical synopsis of the resolution-inducing molecule called resolvin D2. The molecule is a biosynthesized byproduct of docosahexanoic acid (DHA) an ome­ga-3 fatty acid found primarily in blue algae and cold-water fish. The scientists also evaluated resolvin D2 in mice as a treatment for large bow­el-induced sepsis, a serious condition in which the bloodstream is overwhelmed with bacteria. They found resolvin D2 “significantly re­duced the amount of live aerobic bacteria in both blood and perito­ne­um” 12 hours after the large bowel had been breeched. The drop in bacteria coincided with a reduction in total white blood cell levels but, interestingly, with an in­crease in the ratio of monocytes, a specific type of debris-clearing white blood cell. Based on their findings, the authors concluded that re­solvin D2 is a “potent endo­genous mediator” of white blood cells that, importantly, does not shut down the im­mune system.

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