Time Course of the Phenotype of Blood and Bone Marrow Monocytes and Macrophages in the Lung after Cigarette Smoke Exposure In Vivo.

Camila Oliveira Da Silva,Vincent Lagente,Filipe Viana Nascimento,Samuel Dos Santos Valença,Tatiana Victoni,Andréa Monte-Alto-Costa,Luís Pôrto,Mariana Renovato-Martins

doi:10.3390/ijms18091940

Abstract

Alveolar macrophages play a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Monocytes are recruited from blood during inflammation and then mature into alveolar macrophages. The aim of this study was to investigate the effect of cigarette smoke (CS) at different times in lung macrophages and monocytes from blood and bone marrow in mice. Male mice (C57BL/6, n = 45) were divided into groups: control, CS 5 days, CS 14 days and CS 30 days. Five days’ CS exposure induced a pronounced influx of neutrophils and macrophages in the lung associated with increased levels of keratinocyte chemoattractant (KC), tumor necrosis factor-α (TNF-α), nitric oxide (NO) and matrix metalloproteinase (MMP)-12. After 14 days of CS exposure, neutrophil recruitment and cytokine production were greatly reduced. Moreover, chronic CS exposure led to increased recruitment of macrophages (with high expression of CD206), transforming growth factor-β (TGF-β) production as well as no detection of TNF-α, interleukin (IL)-6 and KC. CS can also change the monocyte phenotype in the blood and bone marrow, with an increase in Ly6Clow cells. These results show for the first time that CS can change not only macrophage polarization but also monocyte. These results suggest that continued recruitment of Ly6Clow monocytes may help the distinct renewing macrophage M2 population required for COPD progression.

Highlights

Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by an inflammatory response to inhaled noxious particle gases [1]
Chronic cigarette smoke (CS) exposure led to increased recruitment of macrophages, transforming growth factor-β (TGF-β) production as well as no detection of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and keratinocyte chemoattractant (KC)
These results show for the first time that CS can change macrophage polarization and monocyte

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by an inflammatory response to inhaled noxious particle gases [1]. The major risk factor for COPD, as has been proven in many studies, is exposure to cigarette smoke (CS). It is imputed as the initial trigger for the activation of cells of the innate immune system, such as epithelial cells and macrophages [2]. Alveolar macrophages (AM) play a central role in the pathogenesis of COPD in both the initiation and resolution of the inflammatory response that can alter the normal lung structure [5]. Macrophages have been characterized as classically activated (M1) or alternatively activated (M2) based on surface receptors, gene signatures and secretion of inflammatory mediators. Activated M1 macrophages produce proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), IL-6 and IL-12, whereas M2 macrophages produce anti-inflammatory molecules such as IL-10 and transforming growth factor-β (TGF-β) [7,8,9,10]

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