Increased neutrophil adherence and adhesion molecule mRNA expression in endothelial cells during selenium deficiency.
Leukocyte aggregation and activation on endothelial cells (EC) are important preliminary events in leukocyte migration into tissue and subsequent inflammation. Thus, an increase in leukocyte adherence has the potential to affect inflammatory disease outcome. Selenium (Se) is an integral part of the antioxidant enzyme glutathione peroxidase (GSH-Px) and plays an important role in the maintenance of the redox state of a cell. Se supplementation in the bovine has been shown to improve the outcome of acute mastitis caused by coliform bacteria, in part by enhancing the speed of neutrophil migration into the affected mammary gland. However, the mechanisms by which Se modulates neutrophil migration have not been elucidated. Therefore, an in vitro model of Se deficiency in primary bovine mammary artery EC was used to examine the impact of Se status on the adhesive properties of EC. The effect of Se on functional activities was examined by measuring neutrophil adherence to Se-deficient and Se-supplemented EC. Se-deficient EC showed significantly enhanced neutrophil adherence when stimulated with tumor necrosis factor alpha (TNF-alpha) for 4 or 24 h, interleukin-1 for 12 h, or H2O2 for 20 min (P < 0.05). To determine the mechanisms underlying these changes in neutrophil adherence, the expression of EC adhesion molecules, ICAM-1, E-selectin, and P-selectin were examined at the molecular level by a competitive reverse transcription-polymerase chain reaction. Results revealed higher mRNA expression for E-selectin and ICAM-1 in Se-deficient EC stimulated with TNF-alpha for 3 and 6 h, and greater expression of P-selectin mRNA in Se-supplemented EC with 3-h TNF-alpha stimulation. These studies provide new information to establish the role of Se nutrition in the initiation of leukocyte adherence to endothelium.
Maddox
J F
JF
Department of Veterinary Science, Pennsylvania State University, University Park 16802, USA.
Aherne
K M
KM
Reddy
C C
CC
Sordillo
L M
LM
D000818:Animals; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012643:Selenium / Q000097:blood / Q000172:deficiency* / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D012643:Selenium