Role of recently migrated monocytes in cigarette smoke-induced lung inflammation in different strain of mice

PLoS One. 2013 Sep 13;8(9):e72975. doi: 10.1371/journal.pone.0072975. eCollection 2013.


This study investigates the role of proinflammatory monocytes recruited from blood circulation and recovered in bronchoalveolar lavage (BAL) fluid in mediating the lung damage in a model of acute cigarette smoke (CS)-induced lung inflammation in two strains of mice with different susceptibility to develop emphysema (susceptible -C57BL/6J and non susceptible -129S2/SvHsd). Exposure to whole-body CS for 3 consecutive research cigarettes in one single day induced acute inflammation in the lung of mice. Analysis of BAL fluid showed more influx of recently migrated monocytes at 72 h after CS-exposition in susceptible compared to non susceptible mice. It correlated with an increase in MMP-12 and TNF-α protein levels in the lung tissue, and with an increment of NF-κB translocation to the nucleus measured by electrophoretic mobility shift assay in C57BL/6J mice. To determine the functional role of these proinflammatory monocytes in mediating CS-induced airway inflammation, alveolar macrophages and blood monocytes were transiently removed by pretreatment with intratracheal and intravenous liposome-encapsulated CL2MDP, given 2 and 4 days prior to CS exposure and their repopulation was studied. Monocytes/macrophages were maximally depleted 48 h after last liposome application and subsequently recently migrated monocytes reappeared in BAL fluid of susceptible mice at 72 h after CS exposure. Recently migrated monocytes influx to the lung correlated with an increase in the MMP-12 protein level in the lung tissue, indicating that the increase in proinflammatory monocytes is associated with a major tissue damaging. Therefore our data confirm that the recruitment of proinflammatory recently migrated monocytes from the blood are responsible for the increase in MMP-12 and has an important role in the pathogenesis of lung disease induced by acute lung inflammation. These results could contribute to understanding the different susceptibility to CS of these strains of mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Cell Movement / drug effects*
  • Cell Movement / immunology
  • Clodronic Acid / administration & dosage
  • Gene Expression
  • Liposomes
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / immunology
  • Male
  • Matrix Metalloproteinase 12 / genetics
  • Matrix Metalloproteinase 12 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / pathology
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Nicotiana / adverse effects*
  • Pneumonia / etiology
  • Pneumonia / immunology
  • Pneumonia / pathology
  • Pulmonary Emphysema / etiology
  • Pulmonary Emphysema / immunology
  • Pulmonary Emphysema / pathology*
  • Smoke / adverse effects*
  • Species Specificity
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology


  • Liposomes
  • NF-kappa B
  • Smoke
  • Tumor Necrosis Factor-alpha
  • Clodronic Acid
  • Matrix Metalloproteinase 12

Grants and funding

The work presented was supported by the Spanish “Ministry of Science and Innovation” (SAF2008-05412-C02) and “Spanish Society of Pneumology and Thoracic Surgery” (SEPAR-1002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.