구.추천논문
- 조회2,197
Heedoo Lee*, Duo Zhang*, Debra L. Laskin† and Yang Jin*
*Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA 02118; and †Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854
Address correspondence and reprint requests to Dr. Yang Jin, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, 72 East Concord Street, Boston, MA 02118.
Abstract
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a highly complex process that can be triggered by both noninfectious (sterile) and infectious stimuli. Inflammatory lung responses are one of the key features in the pathogenesis of this devastating syndrome. How ALI/ARDS-associated inflammation develops remains incompletely understood, particularly after exposure to sterile stimuli. Emerging evidence suggests that extracellular vesicles (EVs) regulate intercellular communication and inflammatory responses in various diseases. In this study, we characterized the generation and function of pulmonary EVs in the setting of ALI/ARDS, induced by sterile stimuli (oxidative stress or acid aspiration) and infection (LPS/Gram-negative bacteria) in mice. EVs detected in bronchoalveolar lavage fluid (BALF) were markedly increased after exposure of animals to both types of stimuli. After sterile stimuli, alveolar type-І epithelial cells were the main source of the BALF EVs. In contrast, infectious stimuli–induced BALF EVs were mainly derived from alveolar macrophages (AMs). Functionally, BALF EVs generated in both the noninfectious and infectious ALI models promoted the recruitment of macrophages in in vivo mouse models. Furthermore, BALF EVs differentially regulated AM production of cytokines and inflammatory mediators, as well as TLR expression in AMs in vivo. Regardless of their origin, BALF EVs contributed significantly to the development of lung inflammation in both the sterile and infectious ALI. Collectively, our results provide novel insights into the mechanisms by which EVs regulate the development of lung inflammation in response to diverse stimuli, potentially providing novel therapeutic and diagnostic targets for ALI/ARDS.
논문정보
- Research article
- 2018년 09월 (BRIC 등록일 2020-09-17)
- 국외 연구진
- 생명과학 > 생리학
- 구・추천논문
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