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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:727.)
© 2002 American Heart Association, Inc.

Brief Reviews

Sol Sherry Lecture in Thrombosis

Molecular Events in Acute Inflammation

Stephen M. Prescott; Thomas M. McIntyre; Guy A. Zimmerman; Diana M. Stafforini

From the Huntsman Cancer Institute (S.M.P., D.M.S.), Program in Human Molecular Biology and Genetics (T.M.M., G.A.Z.), and the Departments of Internal Medicine (S.M.P., T.M.M., G.A.Z., D.M.S.), Oncological Sciences (S.M.P.), and Pathology (T.M.M.), University of Utah, Salt Lake City.

Correspondence to Stephen M. Prescott, MD, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112. E-mail steve.prescott{at}hci.utah.edu

The inflammatory response is characterized by a multistep molecular interaction between "signaling" cells, such as endothelial cells, and "responding" cells, such as neutrophils and monocytes. In the first step, selectins produced by signaling cells mediate the tethering of responding cells at sites of inflammation. Subsequently, an additional mediator expressed by signaling cells activates the tethered responding cells. Under pathological conditions, the same mechanism is invoked in inappropriate ways: (1) by prolonged presentation of selectins on the cell surface and (2) by the unregulated production of oxidized phospholipids that mimic the normal secondary signaling molecule, platelet-activating factor (PAF). The enzyme PAF acetylhydrolase (PAF-AH) inactivates PAF and oxidized phospholipids and constitutes an "off" switch that suppresses inflammation. Inhibition of normal PAF-AH function or inactivating mutations of the PAF-AH gene can lead to increased susceptibility to inflammatory disease. These studies have relevance to atherosclerosis and thrombosis, because inflammation is a central feature of both.

Key Words: inflammation • selectins • platelet-activating factor • chemokines • oxidized phospholipids

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