In this section
Critical care involves the care of the sickest patients in the hospital. Critically ill patients have usually been through a significant insult to their body (such as trauma, infection, burn) and have developed organ failure and require life-support. Critical Care is the largest theme bringing together clinicians and scientists from diverse backgrounds and includes collaborative research from hospitals throughout north-west London. Investigations range from evaluating biological mechanisms of organ failure through to the development of innovative technologies which allow the short-term and long-term support and recovery of organs.
Many people are exposed to the environment of an Intensive care unit (ICU) either personally or through a family member. It is often a life-changing event and our work aims to reduce this impact facilitating post-ICU recovery.
@article{Soni:2016:10.1136/thoraxjnl-2015-208032,
author = {Soni, S and Wilson, MR and O'Dea, KP and Yoshida, M and Katbeh, U and Woods, S and Takata, M},
doi = {10.1136/thoraxjnl-2015-208032},
journal = {Thorax},
pages = {1020--1029},
title = {Alveolar macrophage-derived microvesicles mediate acute lung injury},
url = {http://dx.doi.org/10.1136/thoraxjnl-2015-208032},
volume = {71},
year = {2016}
}
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 -