Adhesion molecules on murine brain microvascular endothelial cells: expression and regulation of ICAM-1 and Lgp 55

Abstract

The mechanisms for the initiation of immune reactions in the central nervous system are poorly understood. In this report, we describe the presence of intercellular adhesion molecule-1 (ICAM-1) and Lgp 55 (suggested mouse homologue of human intercellular adhesion molecule-2, ICAM-2) on the surface of brain microvessel endothelium (EN) cells and show in vitro induction of ICAM-1 molecules on EN cells with pro-inflammatory cytokines. ICAM-1 expression was detected using flow cytometry analysis with biotinylated anti-ICAM-1 antibody (YN1/1.7.4). Lgp 55 expression was characterized using PA3 monoclonal antibody. According to our results, 30–40% of the non-activated brain EN cells expressed ICAM-1 and 15–20% expressed Lgp 55 molecules. The ICAM-1 molecule expression was increased after the activation of the cells with recombinant murine gamma interferon (IFN-γ), tumor necrosis factor (TNF-α), and interleukin-1α (IL1-α) in a dose-dependent manner. The increased ICAM-1 expression was detected as early as 2 h following the cytokine treatment and reached its maximum after 24 h. Transforming growth factor-β (TGF-β) did not influence the expression of ICAM-1 molecule. Lgp 55 molecule does not seem to be regulated by pro-inflammatory cytokines. ICAM-1 and Lgp 55 expression was found to be polarized on the luminal surface of EN by confocal laser microscopy suggesting accessibility for leukocytes. Inducible ICAM-1 expression may play a critical role in formation of inflammatory reactions inside the central nervous system.