Alveolar macrophage-derived microvesicles mediate acute lung injury.
Thorax
; 71(11): 1020-1029, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27287089
ABSTRACT
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 1â hour 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 1â hour, the dominant population was alveolar macrophage-derived, and these MVs carried substantive amounts of tumour necrosis factor (TNF) but minimal amounts of IL-1ß/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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Macrófagos Alveolares
/
Micropartículas Derivadas de Células
/
Lesão Pulmonar Aguda
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article