Study of LDL and acetylated LDL endocytosis by mononuclear cells in HIV infection.
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/mm3). On the contrary, in other symptomatic patients (n = 11, CD14+ cells < 100/mm3), 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.
Juompan
L
L
INSERM U 395, Université Paul Sabatier, Toulouse, France.
Puel
J
J
Fournié
G J
GJ
Benoist
H
H
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001667:Binding, Competitive; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D004337:Drug Carriers / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018950:Lipopolysaccharide Receptors; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D011973:Receptors, LDL / Q000378:metabolism; D051116:Receptors, Scavenger
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D004337:Drug Carriers; D018950:Lipopolysaccharide Receptors; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D051116:Receptors, Scavenger; C032629:acetyl-LDL