| Autor: |
Bhuiyan H; Department of Medicine, Clinical Pharmacology Unit, Karolinska Institute, Karolinska University Hospital, Solna, 17176, Stockholm, Sweden., Masquelier M; Department of Medicine, Clinical Pharmacology Unit, Karolinska Institute, Karolinska University Hospital, Solna, 17176, Stockholm, Sweden., Tatidis L; Department of Medicine, Clinical Pharmacology Unit, Karolinska Institute, Karolinska University Hospital, Solna, 17176, Stockholm, Sweden., Gruber A; Centre for Haematology and Regenerative Medicine, Karolinska Institute, Karolinska University Hospital, Solna, 171 76, Stockholm, Sweden., Paul C; Centre for Haematology and Regenerative Medicine, Karolinska Institute, Karolinska University Hospital, Huddinge, 141 86, Stockholm, Sweden., Vitols S; Department of Medicine, Clinical Pharmacology Unit, Karolinska Institute, Karolinska University Hospital, Solna, 17176, Stockholm, Sweden. sigurd.vitols@ki.se. |
| Abstrakt: |
Leukemic cells isolated from most patients with acute myelogenous leukemia (AML) have higher low density lipoprotein (LDL) uptake than normal mononuclear blood cells. Little is known, however, about the mechanism behind the elevated LDL uptake. We investigated if AML cells secrete factors that stimulate cellular LDL uptake. Mononuclear blood cells were isolated from peripheral blood from 42 patients with AML at diagnosis. Cellular LDL uptake was determined from the degradation rate of 125 I-labelled LDL. Conditioned media from AML cells stimulated the LDL degradation in the leukemic cell lines KG1 and HL60, and in isolated AML cells. The stimulatory effect correlated with the LDL degradation in the AML cells directly after isolation from blood. Conditioned media also autostimulated LDL degradation in the AML cells themselves. Concentrations of IL-6 and IL-8 in AML cell conditioned media correlated with the LDL degradation in AML cells directly after isolation from blood. Addition of R-TNF-α, but not IL-6 or IL-8, stimulated LDL degradation in HL60, KG1, and AML cells. The LDL degradation in AML cells could be inhibited by a LDL receptor blocking antibody. AML cells secrete factors that stimulate LDL uptake in a paracrine and autocrine pattern which open up therapeutic possibilities to inhibit the uptake of LDL by administration of antibodies to these factors. |
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