title: Hypercalcemia induces a proinflammatory phenotype in rat leukocytes and endothelial cells.
abstract: Endothelial plasma membrane lipid microdomains, so called lipid rafts/caveolae, are rich in neutral glycosphingolipid, globotriaosylceramide, Gb3Cer, or CD77. Several plasma membrane Ca(2+) channels and pumps are located in lipid rafts/caveolae. Increased Ca(2+) influx could cause the development of an endothelial proinflammatory phenotype. Therefore, the aim of this study was to estimate the effects of hypercalcemia in rats by determination of CD77 expression on CD34+ endothelial cells in the heart, kidney, and vena cava. In addition, potential proinflammatory calcium effect was estimated by CD11b and CD15s expression on leukocytes. To achieve hypercalcemia, Sprague-Dawley male rats were given CaCl2 solution with a concentration of 1.5 % elemental calcium during 14 days. CD77 expression on CD34+ endothelial cells in cell suspensions of the heart, kidney, and vena cava, as well as leukocyte expression of CD11b and CD15s in hypercalcemic and control rats were determined by flow cytometry. Ionized calcium concentration in plasma was 1.37 ± 0.01 mM in hypercalcemic vs. 1.19 ± 0.03 mM in control rats. Hypercalcemic group showed statistically significantly decreased proportion of endothelial CD34+ CD77- cells in the kidney and vena cava in parallel with increase of CD11b and CD15s leukocyte proinflammatory markers. In conclusion, it is tempting to speculate that plasma membranes of glycosphingolipid CD77- endothelial cells are poorer in caveolae lipid microdomains and therefore weaker in controlling of Ca(2+) influx. The percentage of CD11b+ CD15s+ leukocytes could be a measure of proinflammatory effects of mild hypercalcemia.
authors.affiliation: Department of Medical Chemistry and Biochemistry, School of Medicine, University of Split, Split, Croatia.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Režić-Mužinić
authors.forename: Vedrana
authors.initials: V
authors.lastname: Cikeš-Čulić
authors.forename: Joško
authors.initials: J
authors.lastname: Božić
authors.forename: Tina
authors.initials: T
authors.lastname: Tičinović-Kurir
authors.forename: Ilza
authors.initials: I
authors.lastname: Salamunić
authors.forename: Anita
authors.initials: A
authors.lastname: Markotić
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D006934:Hypercalcemia / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D016256:Lewis X Antigen / Q000378:metabolism; D008297:Male; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D014281:Trihexosylceramides / Q000378:metabolism
chemical_list: D018845:CD11 Antigens; D016256:Lewis X Antigen; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D002118:Calcium