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

Int J Mol Sci. 2017 Sep 9;18(9):1940. 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.

Keywords: COPD; cigarette smoke; macrophages; monocytes.

MeSH terms

  • Animals
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Lung / metabolism*
  • Lung / pathology
  • Macrophages / metabolism*
  • Male
  • Mannose Receptor
  • Mannose-Binding Lectins / genetics
  • Mannose-Binding Lectins / metabolism
  • Matrix Metalloproteinase 12 / genetics
  • Matrix Metalloproteinase 12 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / metabolism*
  • Nitric Oxide / metabolism
  • Phenotype*
  • Pulmonary Disease, Chronic Obstructive / etiology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Tobacco Smoke Pollution / adverse effects*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Tobacco Smoke Pollution
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Matrix Metalloproteinase 12