Sol Sherry lecture in thrombosis: molecular events in acute inflammation.
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.
Prescott
Stephen M
SM
Huntsman Cancer Institute, University of Utah, Salt Lake City 84112, USA. steve.prescott@hci.utah.edu
McIntyre
Thomas M
TM
Zimmerman
Guy A
GA
Stafforini
Diana M
DM
D000208:Acute Disease; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D013927:Thrombosis / Q000378:metabolism* / Q000473:pathology*