Uremic serum enhances scavenger receptor expression and activity in the human monocytic cell line U937.
The macrophage scavenger receptor (SR) plays a leading role in atherogenesis, but little is known about the relevance of SR to atherosclerosis in uremia. In this study, the impact of uremic serum on SR expression and activity was examined in the human monocytic cell line U937. The cells were cultured with serum from ten healthy subjects, ten hemodialysis (HD) and ten continuous ambulatory peritoneal dialysis (CAPD) patients. SR mRNA expression was examined using reverse transcriptase-polymerase chain reaction followed by Southern blot. SR protein amount was evaluated by ligand blot. SR activity was analyzed by cellular uptake of fluorescently labeled acetylated low-density lipoprotein using flow cytometry. Uremic serum dose-dependently enhanced SR activity primarily by increasing the amount of receptor protein. Heat-inactivated uremic serum had a stimulatory effect, but ultrafiltrate of uremic serum, which included molecules with a molecular weight less than ten kDa, had no effect. The serum levels of macrophage-colony stimulating factor (M-CSF), an activator of SR, were fourfold higher in uremia and significantly correlated with SR activity in cells treated with uremic serum. Pre-treatment of uremic serum with a neutralizing antibody to M-CSF abolished the effect of uremic serum on SR activity. In conclusion, uremic serum contains a factor(s) that enhances SR expression and activity in U937 cells. Elevated M-CSF in uremic serum could be responsible for this enhancement.
Ando
M
M
Division of Baxter Novum, Department of Clinical Sciences, Huddinge University Hospital, Karolinska Institute, Sweden.
Gåfvels
M
M
Bergström
J
J
Lindholm
B
B
Lundkvist
I
I
D000906:Antibodies; D001161:Arteriosclerosis / Q000209:etiology; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins; D009000:Monocytes / Q000378:metabolism*; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D014511:Uremia / Q000097:blood*
D000906:Antibodies; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D016173:Macrophage Colony-Stimulating Factor