Degranulation of Gastrointestinal Mast Cells Contributes to Hepatic Ischemia-Reperfusion Injury in Mice

The pathological changes following liver damage, including those caused by ischemia and reperfusion (I/R), are closely related to gastrointestinal dysregulation. Mast cells (MCs) are tissue-resident immune cells abundant in the gastrointestinal system that play diverse roles. In view of the characteristic localization of MCs around the microvasculature, we hypothesized that a stimulus-specific set of mediators released through degranulation of gastrointestinal MCs, which are enriched in hepatic sinusoids via the hepatic system, subsequently participate in associated pathological development within the liver. To elucidate the biological role of gastrointestinal MC granules in liver damage, we employed an experimental liver I/R model that allows conditional ablation of MCs. Marked degranulation was detected during I/R, which showed a significant positive correlation with liver damage. Our experiments further disclosed that MC degranulation primarily enhanced the cycle of inflammatory damage in I/R liver consisting of liver sinusoidal endothelial cell (LSEC) death, neutrophil infiltration, and formation of a neutrophil extracellular trap, with a concomitant increase in adhesion molecules, inflammatory cytokines, chemokines and oxidative stress. Based on the collective results, we propose that suppression of activity or number of MCs may present an effective strategy for protection against hepatic I/R injury.

Source: Clinical Science - October 9, 2018 Category: Biomedical Science Authors: He, Z., Li, Y., Ma, S., Yang, M., Ma, Y., Ma, C., Song, J., Yu, T., Zhang, S., Li, J. Tags: PublishAheadOfPrint Source Type: research