TY - JOUR AB - Background Microvesicles (MVs) are important mediators of intercellular communication, packaging a variety of molecular cargo. They have been implicated in the pathophysiology of various inflammatory diseases; yet, their role in acute lung injury (ALI) remains unknown.Objectives We aimed to identify the biological activity and functional role of intra-alveolar MVs in ALI.Methods Lipopolysaccharide (LPS) was instilled intratracheally into C57BL/6 mice, and MV populations in bronchoalveolar lavage fluid (BALF) were evaluated. BALF MVs were isolated 1hour post LPS, assessed for cytokine content and incubated with murine lung epithelial (MLE-12) cells. In separate experiments, primary alveolar macrophage-derived MVs were incubated with MLE-12 cells or instilled intratracheally into mice.Results Alveolar macrophages and epithelial cells rapidly released MVs into the alveoli following LPS. At 1hour, the dominant population was alveolar macrophage-derived, and these MVs carried substantive amounts of tumour necrosis factor (TNF) but minimal amounts of IL-1β/IL-6. Incubation of these mixed MVs with MLE-12 cells induced epithelial intercellular adhesion molecule-1 (ICAM-1) expression and keratinocyte-derived cytokine release compared with MVs from untreated mice (p<0.001). MVs released in vitro from LPS-primed alveolar macrophages caused similar increases in MLE-12 ICAM-1 expression, which was mediated by TNF. When instilled intratracheally into mice, these MVs induced increases in BALF neutrophils, protein and epithelial cell ICAM-1 expression (p<0.05).Conclusions We demonstrate, for the first time, the sequential production of MVs from different intra-alveolar precursor cells during the early phase of ALI. Our findings suggest that alveolar macrophage-derived MVs, which carry biologically active TNF, may play an important role in initiating ALI. AU - Soni,S AU - Wilson,MR AU - O'Dea,KP AU - Yoshida,M AU - Katbeh,U AU - Woods,S AU - Takata,M DO - 10.1136/thoraxjnl-2015-208032 EP - 1029 PY - 2016/// SN - 1468-3296 SP - 1020 TI - Alveolar macrophage-derived microvesicles mediate acute lung injury T2 - Thorax UR - http://dx.doi.org/10.1136/thoraxjnl-2015-208032 UR - http://hdl.handle.net/10044/1/32370 VL - 71 ER -