[Expression and role of Thy-1 on endothelial cells at sites of inflammation--a novel function of Thy-1; vascular permeability regulation].
We investigated the role of surface adhesion molecules in regulating vascular permeability, in vitro and in vivo. Cultured rat endothelial cells (RECs) express Thy-1, intercellular adhesion molecule-1 (ICAM-1), and CD44. Permeability of albumin across the REC monolayer increased through the interaction of Thy-1 and anti-Thy-1 monoclonal antibodies (mAbs), but no increase was seen through ICAM-1 and anti-ICAM-1, CD44 and anti-CD44, and RT1A and anti-RT1A mAbs. The potential of anti-Thy-1 mAb for permeability increase depended on antibody concentration, it peaked at 12h, and was neither mediated by injury nor by growth modulation to the REC monolayer. Effect of anti-Thy-1 mAb was inhibited significantly by the calmodulin antagonist W-7 or the protein kinase inhibitors H-7 and HA-1004, and was completely blocked by the combined addition of W-7 and H-7. It seems likely that both calmodulin and protein kinases are involved in related intracellular signal pathways. Thy-1 expression on RECs was up-regulated with IL-1 beta treatment and was down-regulated with mixed lymphocyte reaction (MLR) supernatant treatment. Although Thy-1 expression on rat vascular endothelium in vivo was not detected, the expression of Thy-1 was induced on dermal endothelial cells at the site of inflammation induced by Freund's complete adjuvant (FCA). Vascular permeability in the inflamed dermis significantly increased when anti-Thy-1 but not anti-ICAM-1, anti-CD44, or anti-RT1A mAbs were given intravenously. The collective evidence suggests that inducible Thy-1 on the endothelium is one important regulatory event in vascular permeability at sites of inflammation.
Second Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
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Ishizu
D000818:Animals; D002147:Calmodulin / Q000502:physiology; D002199:Capillary Permeability; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction; D018800:Thy-1 Antigens / Q000378:metabolism / Q000502:physiology*
D002147:Calmodulin; D007518:Isoantibodies; D018800:Thy-1 Antigens; C035678:anti-Thy antibody; D018799:Intercellular Adhesion Molecule-1