Cell adhesion molecules mediate radiation-induced leukocyte adhesion to the vascular endothelium.
The predominant early histological changes in irradiated tissues are edema and leukocyte infiltration. Cell adhesion molecules (CAMs) are required for the extravasation of leukocytes from the circulation. To study the role of CAMs in the pathogenesis of radiation-mediated inflammation, we quantified the expression of P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 glycoproteins on the surface of irradiated human endothelial cells. We found that E-selectin and ICAM-1 expression increased after irradiation, whereas there was no increased expression of other cytokine-inducible adhesion molecules (P-selectin or vascular cell adhesion molecule-1). We found a dose- and time-dependent increase in radiation-induced expression of both E-selectin and ICAM-1. Furthermore, the threshold dose for E-selectin expression was 1 Gy, whereas the threshold dose for ICAM-1 synthesis was 5 Gy of X-rays. Northern blot analysis of RNA from irradiated endothelial cells demonstrated that ICAM-1 is expressed at 3-6 h following irradiation. No de novo protein synthesis was required for increased ICAM-1 mRNA expression. The 1.1-kb segment of the 5' untranslated region of the ICAM-1 gene was sufficient for X-ray induction of chloramphenicol acetyltransferase reporter gene expression. We measured whether ICAM-1 mediates adhesion of leukocyte to the irradiated endothelium and found that leukocyte adhesion occurred concurrently with ICAM-1 induction. Radiation-mediated leukocyte adhesion was prevented by anti-ICAM-1 blocking antibodies. These data indicate that ICAM-1 participates in the inflammatory response to ionizing radiation. Moreover, radiation induction of these CAMs occurs in the absence of tumor necrosis factor and interleukin 1 production.
Hallahan
D
D
Department of Radiation and Cellular Oncology, Pritzker School of Medicine, University of Chicago, Illinois 60637, USA.
Kuchibhotla
J
J
Wyble
C
C
D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology / Q000528:radiation effects; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000528:radiation effects*; D018922:HL-60 Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000906:Antibodies; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1