Irradiation induced expression of CD31, ICAM-1 and VCAM-1 in human microvascular endothelial cells.
The adherence and migration of leukocytes through the endothelium of blood vessels is an important early event which occurs in normal tissues following ionizing irradiation but the underlying mechanisms are not fully understood. ICAM-1, VCAM-1 and CD31 are membrane proteins of endothelial cells, mediate this process when the vasculature is exposed to other inflammatory stimuli. In this study, expression of ICAM-1, VCAM-1 and CD31 on human dermal microvascular endothelial cells (HDMECs) at 72 hours post-irradiation using flow cytometry and northern analysis was determined. Dose-dependent increases in the surface expression and mRNA of ICAM-1 and CD31 were observed. In contrast VCAM-1 was practically undetectable on both control and irradiated HDMECs but was strongly expressed in TNF-alpha activated positive control HDMECs. The upregulation in ICAM-1 and CD31 was independent of radiation-induced changes in cell size, number and cell cycle stage. We suggest that ICAM-1 is active over a prolonged period whereas VCAM-1 acts only transiently in leukocyte-endothelial interactions in the irradiated microvasculature. The late upregulation of CD31 is a novel finding and may have a function in radiation-induced leukocyte extravasation, platelet adherence to the vascular wall and abnormal endothelial cell proliferation. Both ICAM-1 and CD31 seem to be therapeutic targets for the amelioration of radiation-induced normal tissue damage.
Quarmby
S
S
Department of Pathological Sciences, Medical School, Manchester University M13 9PT, U.K. steven.l.quarmby@man.ac.uk
Hunter
R D
RD
Kumar
S
S
D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000528:radiation effects; D002462:Cell Membrane / Q000378:metabolism / Q000528:radiation effects; D048429:Cell Size / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012867:Skin / Q000098:blood supply; D015854:Up-Regulation / Q000528:radiation effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
D015815:Cell Adhesion Molecules; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1