Unique sensitivities to cytokine regulated expression of adhesion molecules in human heart-derived endothelial cells.
The expression of adhesion molecules by endothelial cells is crucial in many inflammatory processes and plays an active role in the development of reperfusion injury, acute and chronic rejection. The expression of adhesion molecules in different parts of the coronary tree to cytokine stimulation is not known. We describe here a detailed study of the effects of the inflammatory cytokines TNFalpha and IL-1beta on the expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intracellular cell adhesion molecule-1 (ICAM-1) on human aortic root (HAEC), coronary artery (HCAEC) and heart microvascular (HHMEC)) endothelial cells in culture, using flow cytometry. We found constitutive levels of both VCAM-1 and E-Selectin on HCAEC and HHMEC (approximately 20%) which were significantly higher compared to HAEC (approximately 3%). There was an extreme sensitivity of HCAEC and HHMEC to 0.002 ng/ml TNFalpha: (VCAM-1 approximately 40%, E-Selectin approximately 25%) respectively, compared to HAEC (VCAM-1 approximately 5%, E-selectin approximately 5%). IL-1beta showed a similar pattern of expression at low doses (5 U/ml), but was less potent. We also observed prolonged expression of these adhesion molecules, especially on the HHMEC (>48 hours) compared to HAEC. There was also increased binding of peripheral blood mononuclear cells (PBMC) to both non-stimulated and TNFalpha stimulated HCAEC and HHMEC compared to HAEC. This data suggest that endothelial cells in different regions of the coronary tree express different patterns of basal and cytokine-stimulated adhesion molecule expression.
McDouall
R M
RM
NHLI, Department of Cardiothoracic Surgery, Imperial College School of Medicine, Royal Brompton and Harefield NHS Trust, Middlesex, UK.
Farrar
M W
MW
Khan
S
S
Yacoub
M H
MH
Allen
S P
SP
D001013:Aorta, Thoracic / Q000502:physiology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1