ROS- and Radiation Source-Dependent Modulation of Leukocyte Adhesion to Primary Microvascular Endothelial Cells.

Denise Eckert,Franz Rödel,Claudia Fournier,Robert Lehn,Ayele T Tsedeke,Markus Langhans,Stephanie Hehlgans,Felicitas Rapp,Jessica Molendowska

doi:10.3390/cells11010072

Abstract

Anti-inflammatory effects of low-dose irradiation often follow a non-linear dose–effect relationship. These characteristics were also described for the modulation of leukocyte adhesion to endothelial cells. Previous results further revealed a contribution of reactive oxygen species (ROS) and anti-oxidative factors to a reduced leukocyte adhesion. Here, we evaluated the expression of anti-oxidative enzymes and the transcription factor Nrf2 (Nuclear factor-erythroid-2-related factor 2), intracellular ROS content, and leukocyte adhesion in primary human microvascular endothelial cells (HMVEC) upon low-dose irradiation under physiological laminar shear stress or static conditions after irradiation with X-ray or Carbon (C)-ions (0–2 Gy). Laminar conditions contributed to increased mRNA expression of anti-oxidative factors and reduced ROS in HMVEC following a 0.1 Gy X-ray and 0.5 Gy C-ion exposure, corresponding to reduced leukocyte adhesion and expression of adhesion molecules. By contrast, mRNA expression of anti-oxidative markers and adhesion molecules, ROS, and leukocyte adhesion were not altered by irradiation under static conditions. In conclusion, irradiation of endothelial cells with low doses under physiological laminar conditions modulates the mRNA expression of key factors of the anti-oxidative system, the intracellular ROS contents of which contribute at least in part to leucocyte adhesion, dependent on the radiation source.

Highlights

IntroductionEndothelial cells (EC) are transiently activated to bind and recruit leukocytes from the blood stream into tissue [6,7]
Introduction iationsThe endothelium is highly involved in immunological events [1], modulating infections as well as chronic inflammatory diseases, such as atherosclerosis and aging [2,3,4,5].During inflammation, endothelial cells (EC) are transiently activated to bind and recruit leukocytes from the blood stream into tissue [6,7]
We aimed to examine the impact of low doses of X‐rays (0.1 and 0.5 Gy) on the mRNA expression of the transcription factor Nrf2 and the anti‐oxidative enzymes SOD1, GPx1, and Catalase 24 h after pro‐inflammatory stimulation with TNF‐α under more physiological laminar flow shear stress conditions

Summary

Introduction

Endothelial cells (EC) are transiently activated to bind and recruit leukocytes from the blood stream into tissue [6,7]. A critical step in this process is the adhesion, or “trapping”, of leukocytes to the EC to enable subsequent extravasation. In order to bind leukocytes, EC express elevated levels of adhesion molecules like vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1 or E-selectin on their surfaces [8]. Signal transduction is initiated that enables subsequent diapedesis. The expression of adhesion molecules is tightly regulated amongst others, by reactive oxygen species (ROS), which are essential signaling molecules in the regulation of vascular homeostasis [9,10,11].

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