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Mariska Lieuw-a-Fa, Casper Schalkwijk, Victor W.M. van Hinsbergh
Distinct accumulation patterns of soluble forms of E-selectin, VCAM-1 and ICAM-1 upon infusion of TNF in tumor patients
The transmigration of leukocytes across the endothelium is a prerequisite for the inflammatory process. Leukocyte-endothelium interaction is regulated by several endothelial adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Their expression is enhanced by inflammatory mediators, such as TN. In vivo a small part of these adhesion molecules is shed by proteases, and can be detected in the circulation. In this study, the time course of the TN-induced accumulation in the blood of three circulating soluble adhesion molecules, sE-selectin, sICAM-1 and sVCAM-1, was studied in plasma samples of tumor patients enrolled in a phase I trial receiving TN. Two different cohorts were studied. Eleven patients received a continuous 24-hour TN infusion while 10 other patients received a 5-day continuous TN infusion. After 24 hours of TN infusion sE-selectin levels increased by 1985 312 %, sVCAM-1 by 301 19 % and sICAM-1 by 445 82 %. Differences in accumulation patterns were observed after 5 days of continuous TN infusion. sVCAM-1 and sICAM-1 levels showed an increase during the infusion with a maximum at 3 to 5 days and stayed elevated after discontinuation of the TN infusion. In contrast, sE-selectin reached its peak at day 1 and declined thereafter. In conclusion, sVCAM-1 and sICAM-1 show a different accumulation pattern upon TN infusion as compared to sE-selectin in man.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 89, 06/2003
Pages: 1052 - 1057