Na Zhan,Yufeng Wang,Ru Liang,Yousen Wu,Ting Huang,Yuquan Ling,Xinbei Chen,Jiacheng Deng,LiFen Zhou,Kangni Luo,Yilin Cai,Yong-Sheng Tu,Lihui Qu,Jianhua Li
Wood smoke (WS)-derived PM 2.5 is a major environmental risk factor for emphysema, but the role of macrophage-derived exosomes remains unclear. Here, we show that chronic WS exposure in rats induces emphysematous lesions accompanied by markedly increased exosome release, reflected by elevated CD63 expression in alveoli and increased exosome particle number in bronchoalveolar lavage fluid. Pharmacological inhibition of exosome secretion with GW4869 significantly attenuated alveolar destruction. Moreover, intranasal administration of exosomes from PM 2.5 -exposed macrophages was sufficient to recapitulate emphysematous pathology in vivo. Mechanistically, PM 2.5 exposure upregulated the membrane-trafficking protein SNAP23 in macrophages, enhancing exosome secretion and increasing total abundance of ADAM10 within exosomes. Co-localization of CD63 and ADAM10 was observed in alveolar regions of WS-exposed rats and COPD patient lungs. Silencing ADAM10 suppressed caspase-3 activation and reduced epithelial apoptosis, supporting a role for exosomal ADAM10 in driving caspase-3-dependent alveolar epithelial injury. By defining an exosome-mediated macrophage-epithelium pathway that contributes to PM 2.5 -induced emphysema, this study clarifies how combustion-derived PM 2.5 damages lung structure and offers mechanistic insight to reducing the health burden of biomass-related air pollution.
The accumulation of amyloid β (Aβ) containing senile plaques is one of the key histopathological hallmarks of Alzheimer's disease (AD). Increasing evidences demonstrated the important role of autophagy in Aβ clearance. Recent studies implied that extracts from Semiaquilegia adoxoides (DC.) Makino could ameliorate the memory of D-galactose induced aging mice. However, the bioactive substance and underlying mechanism remains unknown. Thus, the present study sought to explore the effects of a novel homogenous peptidoglycane on Aβ 42 secretion and the underlying mechanism. Briefly, we extracted a novel peptidoglycan named SA02C using hot water extraction and alcohol precipitation with the Mw of 13.72 kDa. SA02C contains 73.33% carbohydrate and 27.83% protein. The structure characterization revealed that its glycan part might mainly composed of galacturonic acid with minor rhamnose in backbone, and branched with glucose, galactose, arabinose, xylose and galacturonic acid. The protein or peptide moiety in SA02C was bonded to the polysaccharide via threonine. Bioactivities test showed that SA02C could reduce Aβ 42 production in a dose dependent manner with no obvious cytotoxicity. Mechanism study demonstrated that SA02C could modulate APP processing by upregulating the expression of ADAM10, sAPPα and downregulating BACE1, sAPPβ. Furthermore, SA02C also could stimulate autophagy by promoting the expression of the markers of autophagy such as LC3B and ATG5, resulting in the promotion of Aβ 42 phagocytosis.
危险品化学品经营许可证（带存储）