Expression and function of low-density lipoprotein receptors in CD3-CD16+CD56+ cells: effect of interleukin 2.
Low-density lipoprotein receptors (LDLR) have been shown to be expressed, internalized, and transcribed in CD3-CD16+CD56+ cells. Only a low percentage (up to 12%) of NK cells express LDLR. Interleukin 2 (IL-2) (1000 IU/ml) induced a threefold increase in the expression of LDLR on the cell surface that results from, at least in part, augmentation of LDLR turnover from the cytosol to the membrane. Scatchard analysis revealed that IL-2 decreased the Kd of LDLR binding for LDL from 7.53 to 4.33 nM with an increment in the number of binding sites from 2500 up to 5000. Both the proliferative response and cytotoxic functions of these cells are affected by LDL. Low concentrations of LDL induce an increase in the proliferative response (up to eightfold) and in the cytotoxic response of NK cells (up to fivefold). High concentration (more than 60 micrograms/ml) of LDL hampers both proliferative response and cytotoxic activity of NK cells. LDL did not affect the cytotoxic functions of IL-2-activated NK cells. Overall, we have shown that LDLR is expressed on the surface of NK cells and can be augmented by IL-2. Furthermore, we propose some insights into the mechanism responsible for the enhanced expression of LDLR on NK cell surface. In addition, our data clearly delineate that LDLR plays an important role in the regulation of proliferative responses and cytotoxic activity of these cells.
De Sanctis
J B
JB
Institute of Immunology, Faculty of Medicine, Central University of Venezuela, Sabana Grande, Caracas, Venezuela.
Blanca
I
I
Radzioch
D
D
Bianco
N E
NE
D017252:CD3 Complex / Q000032:analysis*; D019002:CD56 Antigen / Q000032:analysis*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000032:analysis*; D011973:Receptors, LDL / Q000032:analysis* / Q000502:physiology
D017252:CD3 Complex; D019002:CD56 Antigen; D007376:Interleukin-2; D008077:Lipoproteins, LDL; D017452:Receptors, IgG; D011973:Receptors, LDL