Regulation of inflammation: The role of the endothelial cells

Date

1999-08

Journal Title

Journal ISSN

Volume Title

Publisher

Texas Tech University

Abstract

The endothelium plays an important role during the inflammatory response. Through the interaction with leukocytes, endothelial cells (EC) can be exposed to numerous pro-inflammatory mediators including peroxidases resulting in enhancement of the inflammatory process. In this study, EC were exposed to various peroxidases to determine their effects on cytokine secretion and respiratory burst (RB). Chemiluminescence was employed to determine the effects of various peroxidases on EC RB. Recombinant enzymatically inactive human myeloperoxidase (iMPO) and enzymatically inactive horseradish peroxidase(dHRP) increased RB. Enzymatically active porcine eosinophil peroxidase (pEPO) demonstrated a rapid increase in RB followed by no effect over the course of time. Other peroxidases tested had no effect on RB by EC. Recombinant enzymatically active human myeloperoxidase (MPO) and iMPO are derived from neutrophil degranulation and have been reported to augment cytokine secretion by macrophages. Endothelial cells exposed to iMPO in vitro exhibited dose-and time-dependent increases in interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF); however, MPO did not have a significant effect. A ribonuclease protection assay (RPA) indicated this enhancement by iMPO was due to an increase in mRNA levels. Also, EC were exposed to pEPO and an enzymatically inactive fragmented form of human eosinophil peroxidase; both pEPO and fEPO observed a slight decrease in IL-8 secretion by EC. Taken as a whole, these data provide further insight into the effects of peroxidases on the development of inflammation.

Description

Keywords

Inflammation, Endothelium

Citation