Dysregulated Functions of Lung Macrophage Populations in COPD.

Theodore S Kapellos,Anna C Aschenbrenner,Joachim L Schultze,Kevin Bassler,Wataru Fujii

doi:10.1155/2018/2349045

Abstract

Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD.

Highlights

Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema
Three major myeloid cell populations have been identified in the lung which differ in their exact localisation in the tissue and their developmental origin (Figure 1): resident alveolar macrophages (AMs), resident interstitial macrophages (IMs), and blood monocytes [2,3,4]
It is important to advance our knowledge of immune system manifestations in COPD and uncover the molecular pathways responsible for the cross talk between immune cells and the lung stroma in order to provide the clinic with prognosis/diagnosis biomarkers and the pharmaceutical industry with novel testable genes/ pathways for future drug development screenings

Summary

Lung Macrophage Populations in Mice and Humans

The lung is constantly exposed to the host’s outer environment; constitutively active mechanisms are required to monitor for irritants and infections with pathogens. Ly-6ChiCCR2+CX3CR1−GR-1+ monocytes are actively recruited to inflamed tissues where they can differentiate into so-called inflammatory DCs or different flavours of macrophages [60, 63,64,65] This subset was shown to express high levels of chemokine receptors, complement peptides, and annexins, while Ly-6Clo monocytes express more MHC class-II, growth factors, integrins, and scavenger receptors [66, 67]. Infections augment the innate immune responses and lung tissue remodelling in mice [136], while human patients present with dysregulated neutrophil and T cell mobilisation [89, 137], increased proinflammatory mediator levels [138, 139], and antibacterial humoral responses [140]. The study of the functions of lung macrophage populations as well as their interplay with other immune cells and the lung stroma has the potential to enhance our understanding of COPD pathology and provide with novel biomarkers and therapeutic targets

AMs in COPD

IMs and Monocytes in COPD

Findings

Concluding Remarks