Sialyl Lewis X mimetics attenuate E-selectin-mediated adhesion of leukocytes to irradiated human endothelial cells.
Ionizing radiation causes histological changes in normal tissues that resemble those resulting from the inflammatory response. Inflammation is a multistep process requiring expression of adhesion molecules on the surface of endothelial cells which results in leukocyte extravasation. E-selectin is an adhesion molecule that mediates leukocyte "rolling" on the endothelium and is required for the inflammatory response. We quantified E-selectin expression and selectin-dependent adhesion of leukocytes to human endothelial cells after X irradiation to determine whether E-selectin participates in the radiation-mediated inflammation-like response. Immunofluorescence staining of irradiated endothelial cells demonstrated expression of E-selectin on the cell surface similar to that elicited by treatment with interleukin-1 (IL-1). Radiation-mediated expression of E-selectin was dependent on dose and time and occurred at doses as low as 0.5 Gy. Furthermore, the increased adhesion of leukocytes to irradiated endothelial cells was prevented by an E-selectin-blocking antibody. Sialyl Lewis X is one of the molecules on the surface of leukocytes that adheres to E-selectin. The anti-inflammatory agents glycyrrhizin and carminic acid, which are structural analogues of sialyl Lewis X, attenuated adhesion of leukocytes to endothelial cells treated with X rays or IL-1. These data implicate a new class of anti-inflammatory agents in the prevention of adhesions of leukocytes to the irradiated vascular endothelium.
Hallahan
D E
DE
Department of Radiation and Cellular Oncology, Pritzker School of Medicine, University of Chicago, Illinois 60637, USA.
Kuchibhotla
J
J
Wyble
C
C
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002329:Carmine / Q000031:analogs & derivatives / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects*; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology / Q000528:radiation effects*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D018922:HL-60 Cells; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D007962:Leukocytes / Q000502:physiology*; D009844:Oligosaccharides / Q000737:chemistry; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D014965:X-Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019040:E-Selectin; D007375:Interleukin-1; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; D019695:Glycyrrhizic Acid; D002329:Carmine; D006034:Glycyrrhetinic Acid