Zhichen Xing1,2, Junyan Han3,4, Xing Hao1,2, Jinhong Wang1,2, Chunjing Jiang1,2, Yu Hao3,4, Hong Wang1,2, Xueying Wu3,4, Liwei Shen5,6, Xiaojun Dong5,6, Tong Li3,4, Guoli Li3,4, Jianping Zhang3,4, Xiaotong Hou1,2, Hui Zeng3,4. 1. Department of Cardiopulmonary Bypass, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. 2. Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. 3. Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China. 4. Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China. 5. Department of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. 6. Shanghai Institute of Digestive Disease, Shanghai, China.
Abstract
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: Walter J Gomes; Isadora Rocco; Wallace S Pimentel; Aislan H B Pinheiro; Paulo M S Souza; Luiz A A Costa; Marjory M P Teixeira; Leonardo P Ohashi; Caroline Bublitz; Isis Begot; Rita Simone L Moreira; Nelson A Hossne; Guilherme F Vargas; João Nelson R Branco; Carlos A Teles; Eduardo A S Medeiros; Camila Sáfadi; Amândio Rampinelli; Leopoldo Moratelli; Anderson Rosa Rosado; Franciele Kuhn Mesacasa; Ismael Escobar Capriata; Rodrigo Coelho Segalote; Deborah Louize da Rocha Vianna Palmieri; Amanda Cristina Mendes Jardim; Diego Sarty Vianna; Joaquim Henrique de Souza Aguiar Coutinho; João Carlos Jazbik; Henrique Madureira da Rocha Coutinho; Gustavo Kikuta; Zely Sant'Anna Marotti de Almeida; Gibran Roder Feguri; Paulo Ruiz Lucio de Lima; Anna Carolina Franco; Danilo de Cerqueira Borges; Felipe Ramos Honorato De La Cruz; Ulisses Alexandre Croti; Bruna Cury Borim; Carlos Henrique De Marchi; Lilian Goraieb; Karolyne Barroca Sanches Postigo; Fabiano Gonçalves Jucá; Fátima Rosane de Almeida Oliveira; Rafael Bezerra de Souza; Alexandre Cabral Zilli; Raul Gaston Sanchez Mas; Luiz Carlos Bettiati; Ricardo Tranchesi; Ayrton Bertini; Leandro Vieira Franco; Priscila Fernandes; Fabiana Oliveira; Roberto Moraes; Thiago Cavalcanti Vila Nova de Araújo; Otávio Penna Braga; Antônio Cavalcanti Pedrosa; Roberta Tavares Barreto Teixeira; Irla Lavor Lucena Camboim; Eduardo Nascimento Gomes; Pedro Horigushi Reis; Luara Piovan Garcia; Nelson Henrique Goes Scorsioni; Roberto Lago; Solange Guizilini Journal: Braz J Cardiovasc Surg Date: 2021-12-03
Authors: Scott J Denstaedt; Angela C Bustamante; Michael W Newstead; Bethany B Moore; Theodore J Standiford; Rachel L Zemans; Benjamin H Singer Journal: Am J Physiol Lung Cell Mol Physiol Date: 2021-06-23 Impact factor: 6.011