Chromium (VI) increases endothelial cell expression of ICAM-1 and decreases nitric oxide activity.
Occupational, airborne pollutants, such as heavy metals, are recognized for inducing injury and cytotoxicity. Chromium(VI) is a redox cycling heavy metal that has been strongly implicated in the initiation of cancer. Its proinflammatory effects, however, have not been systematically examined. In our study, we found that potassium dichromate [Cr(VI)] treatment of human umbilical vein endothelial cells (HUVEC) increased intracellular adhesion molecule (ICAM) expression at the message level. ICAM message levels remained elevated for 12-24 hours after exposure and increased with time and concentration. Cr(VI) increased the release of superoxide anion without affecting the ability of endothelial cultures to produce nitric oxide. However, Cr(VI) decreased cGMP in HUVEC, suggesting that the nitric oxide produced was scavenged intracellularly. Cr(VI) also increased nitrotyrosine in HUVEC cultures. These data are consistent with the idea that exposure to Cr(VI) increases the production of superoxide anion, which scavenges nitric oxide to increase the formation of peroxynitrite. The loss in nitric oxide activity and increased formation of peroxynitrite likely enhance endothelial cell expression of ICAM-1. Cr(VI)-induced increases in the adhesive properties of the endothelium may play a critical role in the initiation and progression of tissue injury through increased recruitment of proinflammatory white blood cells.
Pritchard
K A
KA
Department of Pathology, Pharmacology & Toxicology, Medical College of Wisconsin, The Cardiovascular Research Center, Milwaukee 53226, USA. kpritch@mcw.edu
Ackerman
A
A
Kalyanaraman
B
B
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011192:Potassium Dichromate / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
D005609:Free Radicals; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; C039642:peroxynitric acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D011192:Potassium Dichromate