Intravascular donor monocytes play a central role in lung transplant ischaemia-reperfusion injury.
Thorax
; 73(4): 350-360, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-28389600
ABSTRACT
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 (2â hours) and reperfusion (2â 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 wetdry 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 72â 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Monócitos
/
Traumatismo por Reperfusão
/
Transplante de Pulmão
Limite:
Animals
Idioma:
En
Revista:
Thorax
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido