Kohara Sho, Ogawa Kazushige
Laboratory of Veterinary Anatomy, College of Life, Environment and Advanced Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano, Osaka 598-8531, Japan.
Laboratory of Veterinary Anatomy, Graduate School of Veterinary Science, Osaka Metropolitan University, 1-58 Rinku-Ourai-Kita, Izumisano, Osaka 598-8531, Japan.
Biomedicines. 2022 Dec 12;10(12):3234. doi: 10.3390/biomedicines10123234.
Kupffer cells are maintained via self-renewal in specific microenvironmental niches, primarily the liver sinusoidal endothelial cells (LSECs). In this study, we propagated tissue-resident macrophages (Mø) from mouse liver using mixed culture with hepatic fibroblastic cells. Propagated liver Mø express , and transcription factors, which are required for Kupffer cell characterization. Thus, Kupffer cell properties are likely to be maintained in liver Mø propagated using mixed culture with fibroblastic cells. We revealed (i) gene expression of certain Eph receptors and ephrin ligands including EphA2, ephrin-A1, EphB4, and ephrin-B1 in propagated liver Mø and primary LSECs, (ii) immunohistochemical localization of these Eph/ephrin member molecules indicating common expression in Kupffer cells and LSECs, and (iii) surface expression of several integrin α and β subunits, including α4β1, αLβ2, αMβ2, and αXβ2 integrin in propagated liver Mø and that of the corresponding ligands ICAM-1 and VCAM-1 in primary LSECs. Moreover, EphA/ephrin-A and EphB/ephrin-B interactions promoted liver Mø adhesion to the ICAM-1-adsorbed surface, which mimicked that of LSECs and may be implicated in the residence of Kupffer cells in the liver sinusoid. Further studies on regulating the residence and regeneration of Kupffer cells in related hepatic disorders are required to validate our findings.
库普弗细胞通过在特定微环境龛中自我更新得以维持，主要是肝窦内皮细胞（LSECs）。在本研究中，我们通过与肝成纤维细胞混合培养从小鼠肝脏中培养出组织驻留巨噬细胞（Mø）。培养出的肝脏Mø表达库普弗细胞特征所需的 、 和 转录因子。因此，使用与成纤维细胞混合培养的方法培养出的肝脏Mø可能维持了库普弗细胞的特性。我们发现：（i）培养出的肝脏Mø和原代LSECs中某些Eph受体和ephrin配体的基因表达，包括EphA2、ephrin-A1、EphB4和ephrin-B1；（ii）这些Eph/ephrin成员分子的免疫组化定位表明在库普弗细胞和LSECs中共同表达；（iii）培养出的肝脏Mø中几种整合素α和β亚基的表面表达，包括α4β1、αLβ2、αMβ2和αXβ2整合素，以及原代LSECs中相应配体ICAM-1和VCAM-1的表面表达。此外，EphA/ephrin-A和EphB/ephrin-B相互作用促进了肝脏Mø对ICAM-1吸附表面的黏附，该表面模拟了LSECs的表面，可能与库普弗细胞在肝窦中的驻留有关。需要对相关肝脏疾病中库普弗细胞的驻留和再生调控进行进一步研究，以验证我们的发现。
