No involvement of alveolar macrophages in the initiation of carbon nanoparticle induced acute lung inflammation in miceReport as inadecuate

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Particle and Fibre Toxicology

, 13:33

First Online: 21 June 2016Received: 10 December 2015Accepted: 10 June 2016DOI: 10.1186-s12989-016-0144-6

Cite this article as: Chen, S., Yin, R., Mutze, K. et al. Part Fibre Toxicol 2015 13: 33. doi:10.1186-s12989-016-0144-6


BackgroundCarbonaceous nanoparticles CNP represent a major constituent of urban particulate air pollution, and inhalation of high CNP levels has been described to trigger a pro-inflammatory response of the lung. While several studies identified specific particle characteristics driving respiratory toxicity of low-solubility and low-toxicity particles such as CNP, the major lung cell type, which initiates and drives that response, remains still uncertain. Since alveolar macrophages AM are known to effectively phagocytose inhaled particles and play a crucial role for the initiation of pulmonary inflammation caused by invading microbes, we aimed to determine their role for sterile stimuli such as CNP by profiling the primary alveolar cell compartments of the lung. We exposed C57BL-6 mice to 20 μg CNP by intratracheal instillation and comprehensively investigated the expression of the underlying mediators during a time span of 3 to 72 h in three different lung cell populations: CD45- negative structural cells, CD45+ positive leukocytes, and by BAL recovered cells.

ResultsBronchoalveolar lavage BAL analysis revealed an acute inflammatory response characterized by the most prominent culmination of neutrophil granulocytes from 12 to 24 h after instillation, which declined to basal levels by day 7. As early as 3 h after CNP exposure 50 % of the AM revealed particle laden. BAL concentrations and lung gene expression profiles of TNFα, and the neutrophil chemoattractants CXCL1,-2 and-5 preceded the neutrophil recruitment and showed highest levels after 12 h of CNP exposure, pointing to a significant activation of the inflammation-evoking lung cells at this point of time. AM, isolated from lungs 3 to 12 h after CNP instillation, however, did not show a pro-inflammatory signature. On the contrary, gene expression analysis of different lung cell populations isolated 12 h after CNP instillation revealed CD45-, mainly representing alveolar epithelial type II ATII cells as major producer of inflammatory CXCL cytokines. Particularly by CD45- cells expressed Cxcl5 proved to be the most abundant chemokine, being 12 h after CNP exposure 24 ±11 fold induced.

ConclusionOur data suggests that AM are noninvolved in the initiation of the inflammatory response. ATII cells, which induced highest CXCL levels early on, might in contrast be the driver of acute neutrophilic inflammation upon pulmonary CNP exposure.

KeywordsCarbonaceous nanoparticles CNP Intratracheal instillation Lung inflammation Sterile inflammation Alveolar macrophage Alveolar epithelial cell Neutrophils Chemokines Electronic supplementary materialThe online version of this article doi:10.1186-s12989-016-0144-6 contains supplementary material, which is available to authorized users.

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Author: Shanze Chen - Renfu Yin - Kathrin Mutze - Youjia Yu - Shinji Takenaka - Melanie Königshoff - Tobias Stoeger


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