Thy-1 induced on rat endothelium regulates vascular permeability at sites of inflammation.
We investigated the role of surface adhesion molecules on endothelial cells in regulating vascular permeability, in vitro and in vivo. Cultured rat endothelial cells (REC) express Thy-1, intercellular adhesion molecule-1 (ICAM-1), CD44 and RT1A. Permeability of albumin across the REC monolayer increased through the interaction of Thy-1 and anti-Thy-1 mAb, but not through ICAM-1 and anti-ICAM-1, CD44 and anti-CD44, and RT1A and anti-RT1A mAb. This anti-Thy-1-effect was completely inhibited when the calmodulin antagonist W-7 and the protein kinase inhibitor H-7 was combined, while the IL-6-mediated increase in REC permeability was blocked by either W-7 or H-7, independently. The anti-Thy-1-mediated permeability increase was additively augmented when IL-6 was admixed. These data suggest that intracellular signaling pathways of anti-Thy-1- and IL-6-mediated permeability regulation may be overlapping to some extent but are largely independent. As anti-Thy-1-treatment generated rearrangement of vimentin filaments within REC, alteration of the cytoskeleton distribution may possibly correlate with the regulation of permeability. Although Thy-1-expression on rat vascular endothelium in vivo was not evident, it was induced at sites of Freund's complete adjuvant-induced dermatitis. The administered anti-Thy-1 mAb exclusively located on vascular endothelial surface at the sites of inflammation. Vascular permeability in inflamed skin tissues was significantly augmented when anti-Thy-1 but not anti-ICAM-1, anti-CD44 or anti-RT1A mAb was administered i.v., without affecting populations of inflammatory cells. The collective evidence suggests that Thy-1 induced on rat endothelium is one important regulatory event in vascular permeability at sites of inflammation.
Ishizu
A
A
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Ishikura
H
H
Nakamaru
Y
Y
Takeuchi
E
E
Kimura
C
C
Koike
T
T
Yoshiki
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D002199:Capillary Permeability / Q000276:immunology* / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D006649:Histocompatibility Antigens / Q000502:physiology; D018960:Hyaluronan Receptors / Q000502:physiology; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D018800:Thy-1 Antigens / Q000096:biosynthesis / Q000502:physiology*
D000911:Antibodies, Monoclonal; D006649:Histocompatibility Antigens; D018960:Hyaluronan Receptors; D018800:Thy-1 Antigens; C038353:histocompatibility antigens RT, rat; D018799:Intercellular Adhesion Molecule-1