Impaired Transmigration of Myeloid-Derived Suppressor Cells across Human Sinusoidal Endothelium Is Associated with Decreased Expression of CD13

Resheq YJ, Menzner AK, Bosch J, Tickle J, Li KK, Wilhelm A, Hepburn E, Murihead G, Ward ST, Curbishley SM, Zimmermann HW, Bruns T, Gilbert D, Tripal P, Mackensen A, Adams DH, Weston CJ (2017)

Publication Type: Journal article

Publication year: 2017

Journal

DOI: 10.4049/jimmunol.1600466

Abstract

Human monocytic myeloid-derived suppressor cells (MO-MDSCs) within the hepatic compartment suppress inflammation and impair immune surveillance in liver cancer. It is currently not known whether recruitment of MO-MDSCs from blood via hepatic sinusoidal endothelium (HSEC) contributes to their enrichment within the hepatic compartment. We compared the transmigratory potential of MO-MDSCs and monocytes after adhesion to hepatic endothelial monolayers in flow-based assays that mimic in vivo shear stress in the sinusoids. Despite comparable binding to HSEC monolayers, proportionally fewer MO-MDSCs underwent transendothelial migration, indicating that the final steps of extravasation, where actin polymerization plays an important role, are impaired in MO-MDSCs. In this article, we found reduced levels of CD13 on MO-MDSCs, which has recently been reported to control cell motility in monocytes, alongside reduced VLA-4 expression, an integrin predominantly involved in adherence to the apical side of the endothelium. CD13 and VLA-4 blocking and activating Abs were used in flow-based adhesion assays, live-cell imaging of motility, and actin polymerization studies to confirm a role for CD13 in impaired MO-MDSC transmigration. These findings indicate that CD13 significantly contributes to tissue infiltration by MO-MDSCs and monocytes, thereby contributing to the pathogenesis of hepatic inflammation.

Authors with CRIS profile

Involved external institutions

University of Birmingham United Kingdom (GB)

How to cite

APA:

Resheq, Y.J., Menzner, A.-K., Bosch, J., Tickle, J., Li, K.-K., Wilhelm, A.,... Weston, C.J. (2017). Impaired Transmigration of Myeloid-Derived Suppressor Cells across Human Sinusoidal Endothelium Is Associated with Decreased Expression of CD13. Journal of Immunology. https://dx.doi.org/10.4049/jimmunol.1600466

MLA:

Resheq, Yazid J., et al. "Impaired Transmigration of Myeloid-Derived Suppressor Cells across Human Sinusoidal Endothelium Is Associated with Decreased Expression of CD13." Journal of Immunology (2017).

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