Effects of lobenzarit disodium on human endothelial cells. Lobenzarit disodium inhibits proliferative response, HLA-DR antigen expression, and T cell adherence toward endothelial cells.
The therapeutic action of lobenzarit disodium (CCA) on the function of endothelial cells (EC) isolated from human umbilical cord veins was investigated. CCA suppressed 3H-thymidine incorporation into EC in a dose-dependent manner. Significant inhibition was detected at a concentration of 50 micrograms/ml. The expression of HLA-DR antigen on the surface of EC was increased when EC were cultured with recombinant interferon-gamma (rIFN gamma). Treatment of EC with either IFN gamma or interleukin-1 enhanced the adhesion of T cells to EC. The kinetics of HLA-DR antigen expression by EC cultured with IFN gamma was different from the kinetics of T cell-EC adhesion, however. Neither anti-HLA-DR nor anti-HLA-ABC monoclonal antibody inhibited T cell binding to EC monolayers. CCA suppressed the expression of HLA-DR antigen by EC cultured with rIFN gamma. In an EC monolayer adhesion assay, CCA also inhibited T cell adhesion to EC in the presence of either IFN gamma or interleukin-1. Significant inhibition was observed at a CCA concentration of 10 micrograms/ml, a level that is easily attainable in serum. These results suggest that CCA may suppress rheumatoid synovitis by reducing the angiogenesis and emigration of chronic inflammatory cells from the blood into the synovium.
Kawakami
A
A
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Ueki
Y
Y
Migita
K
K
Ida
H
H
Nakao
H
H
Kurata
A
A
Fukuda
T
T
Ishimaru
T
T
Kurouji
K
K
D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000166:cytology*; D014471:Umbilical Veins; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D062367:ortho-Aminobenzoates; D007371:Interferon-gamma; C015735:lobenzarit