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@article{Tatham:2018:10.1136/thoraxjnl-2016-208977,
author = {Tatham, KC and O'Dea, KP and Romano, R and Donaldson, HE and Wakabayashi, K and Patel, BV and Thakuria, L and Simon, AR and Sarathchandra, P and POPSTAR, Investigators and Marczin, N and Takata, M},
doi = {10.1136/thoraxjnl-2016-208977},
journal = {Thorax},
pages = {350--360},
title = {Intravascular donor monocytes play a central role in lung transplant ischaemia-reperfusion injury},
url = {http://dx.doi.org/10.1136/thoraxjnl-2016-208977},
volume = {73},
year = {2018}
}

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TY  - JOUR
AB  - Rationale Primary graft dysfunction in lung transplant recipients derives from the initial, largely leukocyte-dependent, ischaemia-reperfusion injury. Intravascular lung-marginated monocytes have been shown to play key roles in experimental acute lung injury, but their contribution to lung ischaemia-reperfusion injury post transplantation is unknown.Objective To define the role of donor intravascular monocytes in lung transplant-related acute lung injury and primary graft dysfunction.Methods Isolated perfused C57BL/6 murine lungs were subjected to warm ischaemia (2hours) and reperfusion (2hours) under normoxic conditions. Monocyte retention, activation phenotype and the effects of their depletion by intravenous clodronate-liposome treatment on lung inflammation and injury were determined. In human donor lung transplant samples, the presence and activation phenotype of monocytic cells (low side scatter, 27E10+, CD14+, HLA-DR+, CCR2+) were evaluated by flow cytometry and compared with post-implantation lung function.Results In mouse lungs following ischaemia-reperfusion, substantial numbers of lung-marginated monocytes remained within the pulmonary microvasculature, with reduced L-selectin and increased CD86 expression indicating their activation. Monocyte depletion resulted in reductions in lung wet:dry ratios, bronchoalveolar lavage fluid protein, and perfusate levels of RAGE, MIP-2 and KC, while monocyte repletion resulted in a partial restoration of the injury. In human lungs, correlations were observed between pre-implantation donor monocyte numbers/their CD86 and TREM-1 expression and post-implantation lung dysfunction at 48 and 72hours.Conclusions These results indicate that lung-marginated intravascular monocytes are retained as a ‘passenger’ leukocyte population during lung transplantation, and play a key role in the development of transplant-associated ischaemia-reperfusion injury.
AU  - Tatham,KC
AU  - O'Dea,KP
AU  - Romano,R
AU  - Donaldson,HE
AU  - Wakabayashi,K
AU  - Patel,BV
AU  - Thakuria,L
AU  - Simon,AR
AU  - Sarathchandra,P
AU  - POPSTAR,Investigators
AU  - Marczin,N
AU  - Takata,M
DO  - 10.1136/thoraxjnl-2016-208977
EP  - 360
PY  - 2018///
SN  - 1468-3296
SP  - 350
TI  - Intravascular donor monocytes play a central role in lung transplant ischaemia-reperfusion injury
T2  - Thorax
UR  - http://dx.doi.org/10.1136/thoraxjnl-2016-208977
UR  - https://thorax.bmj.com/content/73/4/350.info
UR  - http://hdl.handle.net/10044/1/45618
VL  - 73
ER  -

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