Study of LDL and acetylated LDL endocytosis by mononuclear cells in HIV infection

Abstract

Activated lymphocytes have a high level of low density lipoprotein (LDL) uptake as compared to resting lymphocytes, whereas scavenger receptors for acetylated LDL (Ac-LDL) are expressed on limited number of immune cells, i.e., monocytes/macrophages. The endocytosis of LDL and Ac-LDL by mononuclear cells was studied during in vitro and in vivo HIV infection, in order to use LDL and Ac-LDL as carriers of antiviral and/or immunomodulatory drugs towards lymphocytes and monocytes. The uptake of LDL and Ac-LDL was analyzed by cytofluorimetry. LDL endocytosis in PHA/IL2-activated lymphocytes was higher than in resting lymphocytes. In vitro HIV infection of PHA/IL2-activated lymphocytes did not alter the high LDL endocytosis in lymphocytes, CD4 + and CD8 + cells. In a group of 12 symptomatic patients there was no alteration of LDL endocytosis in lymphocytes, CD4 and CD8 lymphocytes. In another group of 23 individuals, the Ac-LDL endocytosis mediated by CD14 + monocytes was unaltered in asymptomatic patients ( n = 6) and in some symptomatic patients ( n = 6, CD14 +cells > 100/mm 3). On the contrary, in other symptomatic patients ( n = 11, CD14 +cells < 100/mm 3), the number of Ac-LDL + CD14 + cells decreased, whereas their efficiency of Ac-LDL endocytosis increased as compared to those of other HIV + patients. In conclusion, the use of lipoproteins as carriers to increase the drug delivery to CD4 + lymphocytes and to CD14 + monocytes can be envisaged, since: (i) the LDL endocytosis was not impaired in CD4 lymphocytes of HIV + patients, and (ii) the Ac-LDL uptake by monocytes was altered only in some patients of stage IV.