P 2 X 7 receptor is required for neutrophil accumulation in a mouse model of irritant contact dermatitis

Irritant contact dermatitis ( ICD ) is an inflammatory reaction caused by chemical toxicity on the skin. The P 2 X 7 receptor ( P 2 X 7 R ) is a key mediator of cytokine release, which recruits immune cells to sites of inflammation. We investigated the role of P 2 X 7 R in croton oil ( C r O )‐induced ICD using in vitro and in vivo approaches. ICD was induced in vivo by C r O application on the mouse ear and in vitro by incubation of murine macrophages and dendritic cells ( DC s) with C r O and ATP . Infiltrating cells were identified by flow cytometry, histology and myeloperoxidase ( MPO ) determination. Effects of the ATP scavenger apyrase were assessed to investigate further the role of P 2 X 7 R in ICD . Animals were also treated with N ‐1330, a caspase‐1 inhibitor, or with clodronate, which induces macrophage apoptosis. C r O application induced severe inflammatory G r1 + cell infiltration and increased MPO levels in the mouse ear. Selective P 2 X 7 R antagonism with A 438079 or genetic P 2 X 7 R deletion reduced the neutrophil infiltration. Clodronate administration significantly reduced G r1 + cell infiltration and local IL ‐1β levels. In vitro experiments confirmed that A 438079 or apyrase treatment prevented the increase in IL ‐1β that was evoked by macrophage and DC incubation with C r O and ATP . These data support a key role for P 2 X 7 in ICD ‐mediated inflammation via modulation of inflammatory cells. It is tempting to suggest that P 2 X 7 R inhibition might be an alternative ICD treatment.