Abstract 14566: The Role of Eosinophils in Pulmonary Hypertension

Abstract

Introduction: Pulmonary hypertension (PH) is a severe life-threatening disease with insidious onset and high mortality, featured by pulmonary vascular remodeling and perivascular inflammatory cell infiltration. However, the precise immune mechanisms underlying PH remain unclear. Although an enhanced Th2 immune response in PH has been reported for years, the role of eosinophils (EOS), one of the Th2 effector cells, in PH is seldom reported. Investigating the roles and molecular mechanisms of EOS may present a novel paradigm of PH development. Hypothesis: EOS protect against PH through lipid metabolites. Methods: EOS infiltration and chemotaxis were investigated in peripheral blood and lung tissues from PH patients and sugen/hypoxia-induced PH mice. ΔdblGATA mice and anti-IL5 antibody (TRFK5)-treated mice were applied to investigate the role of EOS in PH development. Flow cytometry-based assays were used to quantify infiltration of different immune cells. The culture supernatants and lysates of EOS were collected to explore the mechanisms in co-culture cell experiments. Results: EOS accumulated in lung tissues from PH patients and mice, and the infiltration of EOS into pulmonary tissues during PH may be promoted by fibroblast-derived CCL11. Furthermore, EOS deficiency increased neutrophil (p=0.0038) and monocyte/macrophage (p=0.0344) infiltration and promoted pulmonary arterial smooth muscle cell proliferation, leading to aggravated PH in mice. Mechanistically, arachidonate 15-lipoxygenase (ALOX15), which catalyzes the production of pro-resolving lipid mediators, is specifically expressed by EOS. Conclusions: EOS play a beneficial role during PH development via ALOX15 and its downstream lipid mediators, suppressing perivascular inflammation and maintaining smooth muscle cell homeostasis.