Platelet-Activating Factor Regulates Events at the Vascular Wall
Leukocytes must bind to endothelium and migrate into tissues to defend us (for example, against bacterial infection)—the process of physiological inflammation (Zimmerman et al., 1992b). On the other hand, if the activation of leukocytes occurs at the wrong time or place, then pathological changes result. For example, the activation of neutrophils within the blood stream underlies various forms of vascular injury such as the Acute Respiratory Distress Syndrome and reperfusion injury. Additionally, the accumulation of monocytes, and their conversion to macrophages, in the vascular wall is a key feature of atherosclerosis. We have studied the molecular events that regulate adhesion and activation in an in vitro model of these events.
KeywordsEndothelial Cell Acute Respiratory Distress Syndrome Endothelial Cell Surface Adherent Leukocyte Endothelial Cell Response
- Smiley, P.L., Patel, K.D., Stremler, K.E., Zimmerman, G.A., Prescott, S.M., and McIntyre, T.M., 1991, Novel neutrophil agonists: Oxidatively-fragmented phosphatidylcholines. In Prostaglandins, Leukotrienes, Lipoxins, and PAF edited by Bailey, J.M., Plenum Press, New York & London, pp. 269–279.CrossRefGoogle Scholar
- Tjoelker, L.W., Wilder, C., Eberhardt, C., Stafforini, D.M., Dietsch, G., Schimpf, B., Hooper, S., Le Trong, H., Cousens, L.S., Zimmerman, G.A., Yamada, Y., McIntyre, T.M., Prescott, S.M., and Gray, P.W., 1995, Anti-inflammatory properties of a platelet-activating factor acetylhydrolase, Nature 374:549–553.PubMedCrossRefGoogle Scholar
- Weyrich, A.S., McIntyre, T.M., McEver, R.R, Prescott, S.M., and Zimmerman, G.A., 1995, Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-a secretion: Signal integration and NF-kB translocation, J Clin Invest 95:2297-2303 (in press).Google Scholar
- Zimmerman, G.A., Prescott, S.M., and McIntyre, T.M., 1992a, Platelet-activating factor: A fluid-phase and cell-mediator of inflammation. In Inflammation: Basic Principles and Clinical Correlates edited by Gallin, J.I. and Goldstein, I.M., Raven Press, New York, pp. 149–176.Google Scholar