Work

Airway extracellular LTA4H concentrations are governed by release from liver hepatocytes and changes in lung vascular permeability

Year: 2024

Type: article

Abstract: Leukotriene A 4 hydrolase (LTA 4 H) is a bifunctional enzyme, with dual activities critical in defining the scale of tissue inflammation and pathology. LTA 4 H classically operates intracellularly, primarily within myeloid cells, to generate pro-inflammatory leukotriene B 4 . However, LTA 4 H also operates extracellularly to degrade the bioactive collagen fragment proline-glycine-proline to limit neutrophilic inflammation and pathological tissue remodeling. While the dichotomous functions of LTA 4 H are dictated by location, the cellular source of extracellular enzyme remains unknown. We demonstrate that airway extracellular LTA 4 H concentrations are governed by the level of pulmonary vascular permeability and influx of an abundant repository of blood-borne enzyme. In turn, blood LTA 4 H originates from liver hepatocytes, being released constitutively but further upregulated during an acute phase response. These findings have implications for our understanding of how inflammation and repair are regulated and how perturbations to the LTA 4 H axis may manifest in pathologies of chronic diseases.

Source: Cell Reports

DOI: 10.1016/j.celrep.2024.114630