Intravascular donor monocytes play a central role in lung transplant ischaemia-reperfusion injury.

Tatham et al, 2017

Thorax. 2017 Apr 7. pii: thoraxjnl-2016-208977. doi: 10.1136/thoraxjnl-2016-208977. [Epub ahead of print] Intravascular donor monocytes play a central role in lung transplant ischaemia-reperfusion injury.  Tatham KC1, O’Dea KP1, Romano R1,2, Donaldson HE1, Wakabayashi K1, Patel BV1, Thakuria L2, Simon AR2, Sarathchandra P3; Harefield POPSTAR investigators,, Marczin N1,2, Takata M1. (Section of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK. Collaborators (14)

Collaborators: Reed A, De Robertis F, Bahrami T, Amrani M, Popov AF, Mohite PN, Sabashnikov A, Patil NP, Garcia-Saez D, Zych B, Soresi S, Carby M, Dalal P, Griffiths M.


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.


To define the role of donor intravascular monocytes in lung transplant-related acute lung injury and primary graft dysfunction.


Isolated perfused C57BL/6 murine lungs were subjected to warm ischaemia (2 hours) and reperfusion (2 hours) 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.


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 72 hours.


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. ****


Published by the BMJ Publishing Group Limited. . KEYWORDS:Innate Immunity; Lung Transplantation; Macrophage Biology. PMID:28389600 DOI: 10.1136/thoraxjnl-2016-208977 Free full text