Carayon P, Portier M, Dussossoy D, Bord A, Petitprêtre G, Canat X, Le Fur G, Casellas P
Department of Immunology, Sanofi Recherche, Montpelier, France.
Blood. 1996 Apr 15;87(8):3170-8.
Several putative functions have been attributed to the peripheral benzodiazepine receptor (PBR), but its precise physiologic role has not been elucidated. In the present study, we investigated PBR function by quantifying this receptor in leukocyte subsets from healthy donors and in leukemic blasts from lymphoid and myeloid lineages. Using a monoclonal antibody (MoAb) directed against the human PBR and a quantitative flow cytometric assay, we found that phagocytic cells from healthy donors displayed a higher level of PBRs than lymphocytes or natural killer (NK) cells. Among the lymphoid lineage, thymocytes and IgD-negative B cells expressed the lowest levels. However, because of the wide heterogeneity of PBR levels among 42 acute or chronic lymphoid and myeloid leukemias, it was not possible to assign PBR expression to a stage of maturation or a cell lineage. Although the PBR displayed a mitochondrial subcellular localization, its expression was not correlated with the mitochondrial content, suggesting a modulation of PBR density at the level of the mitochondria. This modulation was confirmed when we studied in detail the PBR expression during T-cell development by both flow cytometry and confocal microscopy. We found that the PBR was expressed with a bimodal profile during T-cell development, identical to the one observed with the proto-oncogene, Bcl-2. The high similarity in the expression of both the PBR and the Bcl-2 proto-oncogene in T-cell and B-cell subsets, their common mitochondrial localization, and the observation of high quantities of PBR in phagocytic cells, which are known to produce high levels of radical oxygen species, suggested that PBRs may participate in an antioxidant pathway. Indeed, a strong correlation was established between the ability of hematopoietic cell lines to resist H202 cytotoxicity and their level of PBR expression. Demonstration of the role of PBR in the protection against H202 was obtained by transfecting JURKAT cells with the human PBR cDNA. Transfected cells exhibited increased resistance to H202 compared with wild-type cells, suggesting that PBR may prevent mitochondria from radical damages and thereby modulate apoptosis in the hematopoietic system.
外周苯二氮䓬受体（PBR）具有多种假定功能，但其确切的生理作用尚未阐明。在本研究中，我们通过对健康供体白细胞亚群以及淋巴系和髓系白血病细胞中的该受体进行定量分析，来研究PBR的功能。使用针对人PBR的单克隆抗体（MoAb）和定量流式细胞术分析，我们发现健康供体的吞噬细胞比淋巴细胞或自然杀伤（NK）细胞表现出更高水平的PBR。在淋巴系中，胸腺细胞和IgD阴性B细胞表达水平最低。然而，由于42例急性或慢性淋巴系和髓系白血病中PBR水平存在广泛异质性，因此无法将PBR表达与成熟阶段或细胞系相关联。尽管PBR定位于线粒体亚细胞结构，但它的表达与线粒体含量无关，提示线粒体水平上PBR密度受到调节。当我们通过流式细胞术和共聚焦显微镜详细研究T细胞发育过程中的PBR表达时，这一调节得到了证实。我们发现PBR在T细胞发育过程中呈双峰表达模式，与原癌基因Bcl-2的表达模式相同。PBR和Bcl-2原癌基因在T细胞和B细胞亚群中的表达高度相似、它们共同的线粒体定位，以及已知能产生高水平活性氧的吞噬细胞中存在大量PBR的观察结果，提示PBR可能参与抗氧化途径。事实上，造血细胞系抵抗H2O2细胞毒性的能力与其PBR表达水平之间建立了强相关性。通过用人类PBR cDNA转染JURKAT细胞，证实了PBR在抵抗H2O2中的作用。与野生型细胞相比，转染细胞对H2O2的抗性增加，表明PBR可能防止线粒体受到自由基损伤，从而调节造血系统中的细胞凋亡。
