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2016 ; 71
(11
): 1020-1029
Nephropedia Template TP
Soni S
; Wilson MR
; O'Dea KP
; Yoshida M
; Katbeh U
; Woods SJ
; Takata M
Thorax
2016[Nov]; 71
(11
): 1020-1029
PMID27287089
show ga
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 1?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 1?hour, the dominant
population was alveolar macrophage-derived, and these MVs carried substantive
amounts of tumour necrosis factor (TNF) but minimal amounts of IL-1?/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.
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