Analysis of AT7519 and acetaminophen in a mouse model of acute inflammation by LC-MS/MS

This dataset is the LC-MS/MS analysis of quantities of acetaminophen (APAP) and the drug AT7519 in a preclinical study, as described. Neutrophils are crucial innate immune cells required for host pathogen defense, with multifaceted roles, recognized both in disease pathogenesis and increasingly during tissue repair. Neutrophil actions during acetaminophen (APAP)-induced acute liver injury (ALI), the leading cause of acute liver failure-induced death in the western world, are controversial. Most publications indicate neutrophils contribute to APAP-ALI, but recent reports highlight their reparative function, and no studies evaluate both injury and repair times.
Through a combination of pharmacological (AT7519) neutrophil depletion and genetic prevention of formylated peptide receptor 1 induction of neutrophil activation and chemotaxis, we show that they contribute both to hepatic damage and repair during APAP-ALI. We highlight APAP-ALI neutrophil reparative roles include hepatic extracellular matrix remodeling, angiogenesis and an anti-inflammatory monocyte/macrophage phenotype. This study resolves the time dependent dichotomous role of neutrophils in APAP-ALI, and informs future therapeutic strategies to modulate neutrophil function in APAP-ALI.