Figure 1.

Three models of how PMN contribute to inflammatory resolution: In Model A, transmigrating PMN become activated to consume large amounts of oxygen. As a result, the localized microenvironment becomes hypoxic and culminates in the stabilization of HIF. The activation of multiple HIF target genes (see text) promote the active resolution of inflammation within the mucosa. In Model B, activated PMN and activated platelets (caught in the flow of PMN transmigration) release large amounts of ATP which is subsequently metabolized to adenosine by a two-step enzymatic reaction involving ecto-apyrase (CD39) and ecto-nucleotidase (CD73). Adenosine binding to apical adenosine A2B receptors promotes the resolution of inflammation. In Model C, during epithelial cell-PMN interactions, RvE1 production is amplified by transcellular biosynthesis via the interactions of two or more cell types, each contributing an enzymatic product. In the example shown here, epithelial cell COX-2 generates 18-HEPE from dietary omega-3 PUFA and PMN-expressed 5-LO then generates RvE1. Such locally generated RvE1 is then made available to activate apically expressed ChemR23 which in turn promotes resolution through a number of mechanisms (see text).