Lonicera japonica-Derived Nanovesicles Ameliorate Acute Lung Injury by Suppressing Neutrophil Extracellular Traps Formation in Mice.

Abstract

Acute lung injury (ALI) is a lethal respiratory disease. The inflammatory storm triggered by neutrophil extracellular traps (NETs) is the critical pathogenesis of pulmonary injury. But the effective clinical treatments remain limited for ALI. Hence, developing a pulmonary-targeting nano-drug is urgent in the clinic. Lonicera japonica-derived nanovesicles (LDNVs) was isolated and characterized. Distribution of LDNVs were enriched in the pulmonary neutrophils. LDNVs restored the body weight, physical activity and attenuated the pulmonary injury of LPS-induced ALI mice. The inflammatory cytokines and neutrophil-associated chemokines were decreased with LDNVs treatment. LDNVs also decreased pulmonary accumulation of neutrophils and NETs. The LC3B II was suppressed and p62 was enhanced by LDNVs treatment. Finally, LDNVs suppressed the translocation of LC3 in nuclear and lysosomal damage. But these therapeutic effects of LDNVs in ALI and NETs were both blocked by a neutrophils and NETs activator, phorbol myristate acetate (PMA). LDNVs attenuate LPS-induced ALI by inhibiting NETs formation. These effects may be associated with LDNVs suppressing the autophagic flux.