Effects of selenium supplementation on expression of adhesion molecules in corticoid-dependent asthmatics.
Selenium (Se) deficiency attenuates the host immune response, thereby increasing the risk of bacterial and viral infections. We have examined the effects of selenium supplementation (SeS) in corticoid-dependent asthmatics (CDAs) with lowered circulatory Se status. Twenty CDAs (10 males and 10 females, average age 54.5 yrs) were enrolled into the study. The average duration of the disease was 10 yrs. The asthmatics were receiving 200 micrograms of Se per day for a period of 6 months, in addition to regular treatment with inhaled corticosteroids and beta-agonists. The expression of adhesion molecules (CD11a, CD11b, CD18, CD49d, CD54, CD62L) on peripheral blood mononuclear cells (PBMCs) of asthmatics and the expression of E- and P-selectins, ICAM-1, VCAM-1 on cultured human umbilical vein endothelial cells (HUVEC) after stimulation with PBMCs from CDAs before and after 3 and 6 months of SeS were assessed by standard monoclonal antibodies and analyzed by flow cytometry. The concentrations of soluble adhesion molecules P-selectin, E-selectin, ICAM-1 and VCAM-1 were determined by ELISA method. The expression of adhesion molecules on PBMCs: After 3- and 6-months of SeS, a decreased expression of molecules CD11a, CD11b and CD62L was observed (p < 0.02, p < 0.005, p < 0.003). No changes were seen in the expression of CD18, CD49d except for the increased expression of CD54 (p < 0.005). Modulation of adhesion molecules expression on HUVEC: We observed a significant increase in VCAM-1, P- and E-selectins expressions in the group of asthmatics without SeS in comparison with the control group (p < 0.05, p < 0.01, p < 0.05). During SeS a significant decrease in molecules VCAM-1, E-selectin (after 3 months) (p < 0.05, p < 0.05) and P-selectins and ICAM-1 (after 6 months) (p < 0.05, p < 0.01) were observed. Soluble adhesion molecules: After 3 months of SeS we noticed a significant decrease in VCAM-1 and P-selectin expressions (p < 0.05, p < 0.05) and after 6 months the level of VCAM-1 decreased (p < 0.01). The effect of Se on the adhesion molecules expression in endothelial cells in vitro experiments: Se blocks the expression of adhesion molecules stimulated by IFN-gamma in a dose-dependent way after addition of Se into a culture of endothelial cells. Concentration of 10 micrograms/ml inhibits the increase in expression of ICAM-1 (p < 0.05) but not that of VCAM-1, E- or P-selectins. The inhibition of expression in Se concentration of 10 micrograms/ml is over 80% (p < 0.01). Our data demonstrate that Se is able to affect the adhesion molecules expressions that are crucial in the inflammatory process. (Fig. 5, Ref. 22.)
Jahnova
E
E
Institute of Preventive and Clinical Medicine, Department of Clinical Immunology, Limbova 14, SK-833 01 Bratislava 37, Slovakia. jahnova@upkm.sk
Horvathova
M
M
Gazdik
F
F
Weissova
S
S
D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019087:Selectins / Q000378:metabolism; D012643:Selenium / Q000008:administration & dosage* / Q000494:pharmacology
D000975:Antioxidants; D015815:Cell Adhesion Molecules; D005938:Glucocorticoids; D019087:Selectins; D012643:Selenium