Immunity, inflammation and disease
Methotrexate Modulates Polymorphonuclear Neutrophil Function Through Reduced Chemotaxis and Increased LOX-1 Expression
By Wieke V, Kraus RF, Gruber MA and 1 others.
Abstract
Background
Methotrexate (MTX) is commonly used in patients with autoimmune disorders with the therapeutic objective of inducing immunosuppression predominantly through the modulation of T-lymphocyte activity. Additional studies suggest that the regulation of polymorphonuclear neutrophils (PMNs) may also play a significant role in disease modification. However, the molecular mechanism underlying this effect remains incompletely understood. Moreover, most studies investigating the interaction between MTX and PMNs have relied on centrifugation for cell isolation, a method meanwhile known to alter PMN behavior and activation status itself.
Objectives
The aim of the study was to investigate the effects of MTX on PMN function-including reactive oxygen species (ROS) production, NETosis (Neutrophil Extracellular Traps), and migration-using live-cell imaging, as well as surface epitopes and the respiratory burst assessed by flow cytometry. This comprehensive set of experiments examining the interaction between MTX and PMNs provides a previously unreported level of insight.