Eph/Ephrin Promotes the Adhesion of Liver Tissue-Resident Macrophages to a Mimicked Surface of Liver Sinusoidal Endothelial Cells

Sho Kohara; Kazushige Ogawa

doi:10.3390/biomedicines10123234

Eph/Ephrin Promotes the Adhesion of Liver Tissue-Resident Macrophages to a Mimicked Surface of Liver Sinusoidal Endothelial Cells

Biomedicines. 2022 Dec 12;10(12):3234. doi: 10.3390/biomedicines10123234.

Authors

Sho Kohara¹, Kazushige Ogawa²

Affiliations

¹ Laboratory of Veterinary Anatomy, College of Life, Environment and Advanced Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano, Osaka 598-8531, Japan.
² Laboratory of Veterinary Anatomy, Graduate School of Veterinary Science, Osaka Metropolitan University, 1-58 Rinku-Ourai-Kita, Izumisano, Osaka 598-8531, Japan.

Abstract

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 Id3, Lxra and Spic 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.

Keywords: Eph; ICAM-1; ephrin; integrin; macrophages.

Grants and funding

This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to K.O.; No. 19K06406). The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.