Neutrophils and inflammatory resolution in the mucosa

• Neutrophil accumulation is a hallmark of acute inflammation.
• In the mucosa, neutrophils signal the initiation of resolution.
• Activated neutrophils deplete local oxygen to the extent that HIF is stabilized.
• Mechanisms of inflammatory resolution include the local generation of multiple endogenous signals that culminate in restoration of epithelial barrier.

Inflammatory diseases in mucosal organs as diverse as the lung, liver and intestine inevitably require the intimate interactions between neutrophils and epithelia. The physiologic consequences of such interactions often determine endpoint organ function, and for this reason, much recent interest has developed in identifying mechanisms and novel targets to promote the resolution of mucosal inflammation. Physiologically-relevant in vitro and in vivo model systems have aided in discovery of novel pathways to define basic inflammatory mechanisms and approaches to defining the concepts of inflammatory resolution. Here, we will review the recent literature regarding the contribution of neutrophils to inflammatory resolution, with an emphasis on the role of the tissue microenvironment, endogenous pathways for promoting resolution and the molecular determinants of neutrophil–epithelial cell interactions during ongoing inflammation. These recent studies highlight the dynamic nature of pro-resolving pathways and lend insight into the complexity of treating mucosal inflammation.

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