STUDY OF LDL AND ACETYLATED LDL ENDOCYTOSIS BY MONONUCLEAR-CELLS IN HIV-INFECTION

Activated lymphocytes have a high level of low density lipoprotein (LD L) uptake as compared to resting lymphocytes, whereas scavenger recept ors for acetylated LDL (Ac-LDL) are expressed on limited number of imm une cells, i.e., monocytes/macrophages. The endocytosis of LDL and Ac- LDL by mononuclear cells was studied during in vitro and in vivo HIV i nfection, in order to use LDL and Ac-LDL as carriers of antiviral and/ or immunomodulatory drugs towards lymphocytes and monocytes. The uptak e of LDL and Ac-LDL was analyzed by cytofluorimetry. LDL endocytosis i n PHA/IL2-activated lymphocytes was higher than in resting lymphocytes . In vitro HIV infection of PHA/IL2-activated lymphocytes did not alte r the high LDL endocytosis in lymphocytes, CD4(+) and CD8(+) cells. In a group of 12 symptomatic patients there was no alteration of LDL end ocytosis in lymphocytes, CD4 and CD8 lymphocytes. In another group of 23 individuals, the Ac-LDL endocytosis mediated by CD14(+) monocytes w as 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-L DL endocytosis increased as compared to those of other HIV+ patients. In conclusion, the use of lipoproteins as carriers to increase the dru g delivery to CD4(+) lymphocytes and to CD14(+) monocytes can be envis aged, since: (i) the LDL endocytosis was not impaired in CD4 lymphocyt es of HIV+ patients, and (ii) the Ac-LDL uptake by monocytes was alter ed only in some patients of stage IV.