RT Journal Article
SR Electronic
T1 Intravascular donor monocytes play a central role in lung transplant ischaemia-reperfusion injury
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 350
OP 360
DO 10.1136/thoraxjnl-2016-208977
VO 73
IS 4
A1 Kate Colette Tatham
A1 Kieran Patrick O'Dea
A1 Rosalba Romano
A1 Hannah Elizabeth Donaldson
A1 Kenji Wakabayashi
A1 Brijesh Vipin Patel
A1 Louit Thakuria
A1 Andre Rudiger Simon
A1 Padmini Sarathchandra
A1 Harefield POPSTAR investigators,
A1 Nandor Marczin
A1 Masao Takata
YR 2018
UL http://thorax.bmj.com/content/73/4/350.abstract
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 (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.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 72 hours.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.