.png){kind=icon}
.png){kind=icon}
Return
Mechanical removal of dendritic cell-generating non-classical monocytes via ex vivo lung perfusion
.png){kind=icon}
PRE
AI
DOI：10.1016/j.healun.2014.03.005.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
BACKGROUND: Ex vivo lung perfusion (EVLP) is a novel procedure designed to rapidly assess and recondition unusable donor lungs for transplantation (LTx). EVLP may reduce graft immunogenicity and allorecognition via removal of passenger leukocytes. We aimed to explore this hypothesis using human EVLP and in vitro analysis. METHODS: Explanted human lungs (n = 7) underwent standard EVLP. Perfusate samples and the leukocyte filter were collected, and cells characterized via flow cytometry. Isolated alveolar monocytes (from post-LTx bronchoalveolar lavage) were differentiated to dendritic cells and characterized (n = 10). An in vitro (air epithelial liquid endothelial) lung model was utilized to evaluate monocyte migration and differentiation within the lung. RESULTS: Non-classical monocytes (NCM, normally <1% of total white blood cell repertoire) mobilized within 30 minutes of EVLP and represented 80.04% of the passenger leukocyte population. This subset readily differentiated to dendritic cells and secreted pro-inflammatory cytokines (interferon-gamma and interleukin-2) after stimulation. NCM rapidly diapedesed from the vascular bed to the alveolus and, when cultured on the alveolus, differentiated to dendritic cells with inflammatory phenotypes. CONCLUSIONS: The lung possesses a reservoir of NCM, which can readily diapedese to the alveolus or mobilize in the circulation. After activation, NCM differentiate to inflammatory dendritic cells with T-cell co-stimulatory capacity. EVLP may impart additional benefits after LTx via the removal of passenger monocytes, which may represent a previously unidentified beneficial mechanism of action. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved.
Keywords:
lung transplantation
ex vivo lung perfusion
monocyte
dendritic cell
passenger leukocytes
diapedesis
non-classical monocyte
Journal
IF:
6
Papers:
1.4W
Citations:
1.4W