Double-Hit-Induced Leukocyte Extravasation Driven by Endothelial Adherens Junction Destabilization
JOURNAL OF IMMUNOLOGY
Authors: Morsing, Sofia K. H.; Al-Mardini, Claudia; van Stalborch, Anne-Marieke D.; Schillemans, Maaike; Bierings, Ruben; Vlaar, Alexander P.; van Buul, Jaap D.
Abstract
During inflammation, endothelial cells are bombarded with cytokines and other stimuli from surrounding cells. Leukocyte extravasation and vascular leakage are both prominent but believed to be uncoupled as they occur in separate spatiotemporal patterns. In this study, we investigated a "double-hit" approach on primary human endothelial cells primed with LPS followed by histamine. Using neutrophil transendothelial migration (TEM) under physiological flow assays, we found that an LPS-primed endothelium synergistically enhanced neutrophil TEM when additionally treated with histamine, whereas the effects on neutrophil TEM of the individual stimuli were moderate to undetectable. Interestingly, the double-hit-induced TEM increase was not due to decreased endothelial barrier, increased adhesion molecule expression, or Weibel-Palade body release. Instead, we found that it was directly correlated with junctional remodeling. Compounds that increased junctional "linearity" (i.e., stability) counteracted the double-hit effect on neutrophil TEM. We conclude that a compound, in this case histamine (which has a short primary effect on vascular permeability), can have severe secondary effects on neutrophil TEM in combination with an inflammatory stimulus. This effect is due to synergic modifications of the endothelial cytoskeleton and junctional remodeling. Therefore, we hypothesize that junctional linearity is a better and more predictive readout than endothelial resistance for compounds aiming to attenuate inflammation.
Central mechanisms of itch: A systematic literature review and meta-analysis
JOURNAL OF NEURORADIOLOGY
Authors: Najafi, Peyman; Carre, Jean-Luc; Ben Salem, Douraied; Brenaut, Emilie; Misery, Laurent; Dufor, Olivier
Abstract
In recent years, studying the central mechanism of itch has gained momentum. However, a proper meta-analysis has not been conducted in this domain. In this study, we tried to respond to this need. A systematic search and a meta-analysis were carried out to estimate the central mechanism of itch. The itch matrix comprises the thalamus and the parietal, secondary somatosensory, insular and cingulate cortices. We have shown that the basal ganglia (BG) play an important role in itch reduction. Finally, we explored itch processing in AD patients and observed that the itch matrix in these patients was different. In conclusion, this is the first meta-analysis on the central mechanisms of itch perception and processing. Our study demonstrated that different modalities of itch induction can produce a common pattern of activity in the brain and provided further insights into understanding the underlying nature of itch central perception. (C) 2019 Published by Elsevier Masson SAS.