Role of monocytes and macrophages in regulating immune response following lung transplantation

Abstract

Purpose of review: Advances in the field of monocyte and macrophage biology have dramatically changed our understanding of their role during homeostasis and inflammation. Here we review the role of these important innate immune effectors in the lung during inflammatory challenges including lung transplantation.

Recent findings: Neutrophil extravasation into lung tissue and the alveolar space have been shown to be pathogenic during acute lung injury as well as primary graft dysfunction following lung transplantation. Recent advances in lung immunology have demonstrated the remarkable plasticity of both monocytes and macrophages and demonstrated their importance as mediators of neutrophil recruitment and transendothelial migration during inflammation.

Summary: Monocytes and macrophages are emerging as key players in mediating both the pathogen response and sterile lung inflammation, including that arising from barotrauma and ischemia-reperfusion injury. Ongoing studies will establish the mechanisms by which these monocytes and macrophages initiate a variety of immune response that lay the fundamental basis of injury response in the lung.

Figure 1

Role of Lung Monocytes and Macrophages in Homeostasis, Bacterial Infection, Barotrauma, and Ischemia-Reperfusion Injury/PGD. (A) In homeostasis, lung non-classical monocytes patrol the endothelium, while classical monocytes survey the parenchyma. Classical monocytes can differentiate into interstitial macrophages or monocyte-derived dendritic cells, or remain undifferentiated while monitoring for infection or injury signals. Alveolar macrophages are resident in the lung, independent from monocytes and remain in the alveolar space. (B) During pathogen challenge in the alveolar space, alveolar macrophages are the first to be activated, releasing chemokines and cytokines which then recruit monocytes and neutrophils. Neutrophils, on arrival to the site of infection, are capable of degranulating and generating neutrophil extracellular traps in an effort to combat infection. (C) During mechanical ventilation, stretch-induced injury activates endothelium, alveolar macrophages, and epithelium, causing recruitment and activation of both classical and non-classical monocytes and the recruitment of neutrophils. (D) During ischemia-reperfusion, alveolar macrophages and monocytes become activated, recruiting neutrophils, and if the injury is severe enough, they can lead to primary graft dysfunction.