Distinct accumulation patterns of soluble forms of E-selectin, VCAM-1 and ICAM-1 upon infusion of TNFalpha 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 TNalpha. 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 TNalpha-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 TNalpha. Two different cohorts were studied. Eleven patients received a continuous 24-hour TNalpha infusion while 10 other patients received a 5-day continuous TNalpha infusion. After 24 hours of TNalpha 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 TNalpha 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 TNalpha 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 TNalpha infusion as compared to sE-selectin in man.
Lieuw-a-Fa
Mariska
M
Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
Schalkwijk
Casper
C
van Hinsbergh
Victor W M
VW
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000187:drug effects*; D017321:Clinical Trials, Phase I as Topic; D015331:Cohort Studies; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007700:Kinetics; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1