Subcellular localization of peripheral benzodiazepine receptors on human leukocytes.
BACKGROUND
The peripheral-type benzodiazepine receptor (PBR) was initially identified in many peripheral tissues and in some blood cells. Drugs that bind with high affinity to PBRs have previously been described as having immunomodulating properties. The number of PBRs varies according to the cell population considered. The aim of this study was to study the localization of PBRs in two human leukocyte populations, T4-lymphocytes, and monocytes.


METHODS
Both cell populations were purified by negative immunoselection in order to keep only the physiologically accessible sites on the viable cells. Mitochondria were quantified by electron microscopy and flow cytometric analysis. Subcellular localization was then studied after PBR photoaffinity labeling using electron microscopic ultrastructural autoradiography.


RESULTS
We have shown that monocytes contain twice as many mitochondria as lymphocytes. We have also shown that the global labeling of monocytes by ultrastructural autoradiography is actually higher than that of lymphocytes and the labeling of monocyte mitochondria is higher than that of lymphocyte mitochondria. In addition, the distribution of subcellular labeling indicates that there are different populations of mitochondria in one cell, i.e., labeled and unlabeled, and that the percentage of labeled mitochondria is greater in monocytes. These results are consistent with those obtained in previous binding studies. Finally, over 50% of receptors are localized in cell compartments devoid of visible mitochondria.


CONCLUSIONS
The subcellular distribution of the PBR shows that this receptor could have other physiologic functions towards immune cells than a function associated with mitochondria.
Cahard
D
D
Toxicology Department, Elf-Sanofi Recherche, Montpellier, France.
Canat
X
X
Carayon
P
P
Roque
C
C
Casellas
P
P
Le Fur
G
G
D001345:Autoradiography; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007107:Immune System / Q000502:physiology; D007425:Intracellular Membranes / Q000737:chemistry / Q000648:ultrastructure; D007962:Leukocytes / Q000737:chemistry* / Q000166:cytology / Q000648:ultrastructure; D008854:Microscopy, Electron; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D011963:Receptors, GABA-A / Q000032:analysis* / Q000502:physiology; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure
D011963:Receptors, GABA-A