The Role of Connexin 43 and Pannexin 1 During Acute Inflammation.

Petra Kameritsch,Kristin Pogoda

doi:10.3389/fphys.2020.594097

Abstract

During acute inflammation, the recruitment of leukocytes from the blood stream into the inflamed tissue is a well-described mechanism encompassing the interaction of endothelial cells with leukocytes allowing leukocytes to reach the site of tissue injury or infection where they can fulfill their function such as phagocytosis. This process requires a fine-tuned regulation of a plethora of signaling cascades, which are still incompletely understood. Here, connexin 43 (Cx43) and pannexin 1 (Panx1) are known to be pivotal for the correct communication of endothelial cells with leukocytes. Pharmacological as well as genetic approaches provide evidence that endothelial Cx43-hemichannels and Panx1-channels release signaling molecules including ATP and thereby regulate vessel function and permeability as well as the recruitment of leukocytes during acute inflammation. Furthermore, Cx43 hemichannels and Panx1-channels in leukocytes release signaling molecules and can mediate the activation and function of leukocytes in an autocrine manner. The focus of the present review is to summarize the current knowledge of the role of Cx43 and Panx1 in endothelial cells and leukocytes in the vasculature during acute inflammation and to discuss relevant molecular mechanisms regulating Cx43 and Panx1 function.

Highlights

During acute inflammation the recruitment of leukocytes from the bloodstream to the site of injury or infection is a highly regulated mechanism to ensure that leukocytes leave the bloodstream at the inflammatory site to eliminate the inflammatory trigger (Nourshargh and Alon, 2014)
In another study it was shown that treatment of endothelial cells (EC) with peptidoglycan, a gram-positive bacterial cell wall component, induced ATP-release via connexin 43 (Cx43)-hemichannel opening which elicited a pro-inflammatory response by induction of interleukin 6 and Toll-like receptor 2 expression (Robertson et al, 2010), both known to be involved in leukocyte recruitment (Jones, 2005; Sabroe et al, 2005)
Peptides have been shown to be transferred via Gap junction channels (GJ) between cells causing recognition of nearby bystander cells and activated monocytes by cytotoxic T-cells (Neijssen et al, 2005). The activity of both Cx43-hemichannels and pannexin 1 (Panx1)-channels depends on diverse environmental stimuli and increases under pathophysiological conditions including acute inflammation

Summary

Introduction

During acute inflammation the recruitment of leukocytes from the bloodstream to the site of injury or infection is a highly regulated mechanism to ensure that leukocytes leave the bloodstream at the inflammatory site to eliminate the inflammatory trigger (Nourshargh and Alon, 2014). In vitro studies confirmed a reduced adhesion of activated neutrophils to EC or alveolar epithelial cells with blocked Cx43-containing GJ, which are both involved in LPS-induced lung inflammation.

Results

Conclusion