Bucillamine inhibits T cell adhesion to human endothelial cells.
We investigated the ability of bucillamine [N-(2-mercapto-2-methyl-propionyl)-L-cysteine] to prevent T cell adhesion to endothelial cells (EC) isolated from human umbilical vein. When EC were pretreated with bucillamine, T cell binding to the EC was suppressed in a dose dependent fashion. The T cells could bind preferentially to recombinant interferon-gamma (rIFN-gamma) treated EC compared with untreated EC. Bucillamine could also suppress T cell binding to rIFN-gamma treated EC as well as untreated EC. Addition of copper sulfate to bucillamine decreased significantly the percent T cell adhesion to the EC compared with bucillamine alone. The magnitude of inhibition by bucillamine and copper sulfate was similar in EC treated with rIFN-gamma as well as in untreated EC. H2O2 also inhibited the T cell binding to both untreated and rIFN-gamma treated EC. The inhibitory effects of bucillamine with or without copper sulfate on T cell binding to EC were abolished completely by catalase but not by superoxide dismutase. Our results suggest that hydrogen peroxide generated by bucillamine, with or without copper sulfate, inhibits T cell binding to EC. We believe, therefore, that bucillamine may suppress inflammation, such as that in rheumatoid synovitis, by reducing the emigration of chronic inflammatory cells from capillaries into tissue.
Eguchi
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Kawakami
A
A
Ida
H
H
Nakashima
M
M
Yamashita
I
I
Sakai
M
M
Shimada
H
H
Terada
K
K
Fukuda
T
T
Ishimaru
T
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002374:Catalase / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology; D019327:Copper Sulfate; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D011994:Recombinant Proteins; D013482:Superoxide Dismutase / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011994:Recombinant Proteins; D003300:Copper; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D003545:Cysteine; D019327:Copper Sulfate; C026535:bucillamine