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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:353.)
© 2000 American Heart Association, Inc.

Vascular Biology

Adhesion of Monocyte Very Late Antigen-4 to Endothelial Vascular Cell Adhesion Molecule-1 Induces Interleukin-1ß–Dependent Expression of Interleukin-6 in Endothelial Cells

Dietlind Zohlnhöfer; Korbinian Brand; Katharina Schipek; Gisela Pogatsa-Murray; Albert Schömig; Franz-Josef Neumann

From the 1. Medizinische Klinik and Deutsches Herzzentrum and Institut für Klinische Chemie und Pathobiochemie (K.B.), Technische Universität München, Germany.

Correspondence to Dietlind Zohlnhöfer, MD, Deutsches Herzzentrum und 1. Medizinische Klinik der Technischen Universität München, Lazarettstraße 36, D-80636 München, Germany. E-mail dietlind.zohlnhoefer{at}micromet.de

Abstract—In atheroma, T cell–derived interferon- (INF-) stimulates endothelial cells and facilitates recruitment of monocytes. We investigated potential mechanisms by which these interactions could contribute to local and systemic inflammatory responses. Specifically, we analyzed the expression of interleukin (IL)-1ß and IL-6 in both cell types after coculture, the relevant adhesion molecules in this interaction, and transcriptional control by NF-B. We studied coculture of purified peripheral blood monocytes with human umbilical vein endothelial cells (HUVECs), which were stimulated with INF- (10⁶ U/L) to model the activated endothelium of atherosclerotic lesions. Coculture of monocytes with activated HUVECs resulted in release of IL-1ß (40.6±3 pg/24 h, P=0.002) and IL-6 (46.6±7 ng/24 h, P=0.0015). Electrophoretic mobility gel shift assay and Northern blotting in each cell type separately revealed NF-B activation in both cell types, IL-1ß mRNA expression predominantly in monocytes, and IL-6 mRNA expression predominantly in HUVECs. The endothelial IL-6 release was IL-1–dependent, because it was suppressed by IL-1 receptor antagonist. Experiments with blocking antibodies demonstrated that binding of monocyte very late antigen-4 (VLA-4) to endothelial vascular cell adhesion molecule-1 (VCAM-1) was necessary for the induction of IL-1ß in monocytes. Binding of monocyte VLA-4 to endothelial VCAM-1 induces NF-B activation in both cell types with expression and release of IL-1ß by monocytes, which in turn stimulates endothelial release of IL-6. The ß₁-integrin–mediated expression of IL-1ß and IL-6 could contribute to local and systemic inflammatory reactions in atherosclerosis.

Key Words: monocyte • endothelial cell • ß₁-integrin • interleukin-1ß • interleukin-6

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