Instillation of particulate matter 2.5 induced acute lung injury and attenuated the injury recovery in ACE2 knockout mice

Abstract

Inhaled particulate matter 2.5 (PM _2.5) can cause lung injury by inducing serious inflammation in lung tissue. Renin-angiotensin system (RAS) is involved in the pathogenesis of inflammatory lung diseases and regulates inflammatory response. Angiotensin-converting enzyme II (ACE2), which is produced through the angiotensin-converting enzyme (ACE)/angiotensin II (Ang II) axis, protects against lung disease. However, few studies have focused on the relationships between PM _2.5 and ACE2. Therefore, we aimed to explore the role of ACE2 in PM _2.5-induced acute lung injury (ALI). An animal model of PM _2.5-induced ALI was established with wild type (C57BL/6, WT) and ACE2 gene knockout (ACE2 KO) mice. The mice were exposed to PM _2.5 through intratracheal instillation once a day for 3 days (6.25 mg/kg/day) and then sacrificed at 2 days and 5 days after PM _2.5 instillation. The results show that resting respiratory rate (RRR), levels of inflammatory cytokines, ACE and MMPs in the lungs of WT and ACE2 KO mice were significantly increased at 2 days postinstillation. At 5 days postinstillation, the PM _2.5-induced ALI significantly recovered in the WT mice, but only partially recovered in the ACE2 KO mice. The results hint that PM _2.5 could induce severe ALI through pulmonary inflammation, and the repair after acute PM _2.5 postinstillation could be attenuated in the absence of ACE2. Additionally, our results show that PM _2.5-induced ALI is associated with signaling p-ERK1/2 and p-STAT3 pathways and ACE2 knockdown could increase pulmonary p-STAT3 and p-ERK1/2 levels in the PM _2.5-induced ALI.