Vanderkerken K, Bouwens L, De Neve W, Van den Berg K, Baekeland M, Delens N, Wisse E
Laboratory for Cell Biology and Histology, Free University of Brussels (V.U.B.), Belgium.
Hepatology. 1993 Oct;18(4):919-25. doi: 10.1002/hep.1840180425.
Liver sinusoids contain a population of large granular lymphocytes or natural killer cells, originally termed pit cells. After isolation and purification, these cells were separated into a low-density and a high-density fraction. The liver low-density fraction differs significantly in morphology and function from cells of the blood, whereas the liver high-density fraction shows intermediate properties. In this study we demonstrate that this morphological and functional heterogeneity is based on subsequent steps of differentiation of the large granular lymphocytes within the liver. When cell proliferation was suppressed by sublethal total body irradiation, the life span of the hepatic large granular lymphocytes could be determined: high-density and low-density populations were totally depleted within 1 and 2 wk after irradiation, respectively. By using intravenous asialo-GM1 anti-serum to deplete animals of asialo-GM1-positive cells, we found that the depletion of the asialo-GM1-positive cells preceded the depletion of asialo-GM1-negative hepatic low-density large granular lymphocytes by approximately 1 wk. Direct evidence that the asialo-GM1-positive high-density large granular lymphocytes are precursors of the low-density large granular lymphocytes was given by adoptive transfer experiments with fluorescent-labeled high-density cells. Three days after their injection, labeled large granular lymphocytes were found in the hepatic low-density fraction of the recipient rat, and these cells had developed morphological characteristics of low-density large granular lymphocytes. It is concluded therefore that marginating blood large granular lymphocytes differentiate through high-density large granular lymphocytes into the typical liver specific low-density large granular lymphocytes or pit cells.
肝血窦含有一群大颗粒淋巴细胞或自然杀伤细胞，最初被称为肝窦周细胞。分离纯化后，这些细胞被分成低密度和高密度组分。肝低密度组分在形态和功能上与血液中的细胞有显著差异，而肝高密度组分则表现出中间特性。在本研究中，我们证明这种形态和功能的异质性是基于肝内大颗粒淋巴细胞分化的后续步骤。当通过亚致死性全身照射抑制细胞增殖时，可确定肝大颗粒淋巴细胞的寿命：照射后1周和2周内，高密度和低密度群体分别完全耗竭。通过使用静脉注射去唾液酸GM1抗血清耗尽动物体内去唾液酸GM1阳性细胞，我们发现去唾液酸GM1阳性细胞的耗竭比去唾液酸GM1阴性肝低密度大颗粒淋巴细胞的耗竭提前约1周。用荧光标记的高密度细胞进行过继转移实验，直接证明了去唾液酸GM1阳性高密度大颗粒淋巴细胞是低密度大颗粒淋巴细胞的前体。注射后三天，在受体大鼠的肝低密度组分中发现了标记的大颗粒淋巴细胞，这些细胞具有低密度大颗粒淋巴细胞的形态特征。因此可以得出结论，边缘血大颗粒淋巴细胞通过高密度大颗粒淋巴细胞分化为典型的肝脏特异性低密度大颗粒淋巴细胞或肝窦周细胞。
