Background As immune regulatory and effector cells, monocytes play an important role in the blood–extracorporeal circuit contact-related acute lung injury in patients undergoing cardiopulmonary bypass (CPB). However, circulating monocytes are phenotypically and functionally heterogeneous, so we characterised how immature monocytes affect acute lung injury induced by CPB.
Methods The identification and dynamic changes in monocyte subsets were monitored by flow cytometry in patients undergoing CPB and in a rat model of CPB. The differentiation and migration of monocyte subsets were explored by in vitro cultures and adoptive transfer in the CPB rat model.
Results We observed a dramatic increase of two monocyte subsets in the peripheral blood of patients undergoing CPB, involving tumour necrosis factor (TNF)-α-producing, mature intermediate CD14highCD16+ monocytes and a novel immature CD14lowCD16− subset. The immature CD14lowCD16− monocytes possessed limited ability for TNF-α production, and failed to suppress T-cell proliferation mediated by T-cell receptor signalling. However, these immature cells were highly proliferative and could differentiate into TNF-α producing, mature CD14highCD16+ monocytes. In the rat model of CPB, we further demonstrated that CPB induced migration of immature monocytes into the lungs, either from the bone marrow or from the spleen. Moreover, we confirmed the hypothesis that immature subsets could contribute to CPB-induced acute lung injury by giving rise to TNF-α producing descendants.
Conclusions The immature CD14lowCD16− monocytes might contribute to blood-circuit contact-induced acute lung injury by generating TNF-α-producing, mature monocytes. New strategies based on monocyte manipulation could be a promising therapeutic approach for minimising CPB-related lung injury.
- Macrophage Biology
- Innate Immunity
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ZX, JH, and XH contributed equally to this paper.
Contributors Study concept and design: XH and HZ; acquisition of data: ZX, JH, XH, JW, CJ, YH, XW, LS, XD and TL; analysis and interpretation of data: ZX, JH, XH, HW, GL and JZ; first drafting of the manuscript: ZX, JH and XH; critical revision of the manuscript for important intellectual content: all authors; study supervision: XH and HZ; data access and responsibility: XH and HZ had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis and for the submission.
Funding The authors received support from the National Natural Science Foundation of China (grant Nos. 81071587 to ZH, 81070203, 81270327 to HXT).
Competing interests None declared.
Patient consent Obtained.
Ethics approval All human blood samples were collected with written informed consent, and the study conformed to the tenets of the Declaration of Helsinki.
Provenance and peer review Not commissioned; externally peer reviewed.