VCAM-1-mediated neutrophil infiltration exacerbates ambient fine particle-induced lung injury

Anfeng Cui, Meng Xiang, Ming Xu, Peng Lu, Shun Wang, Yajuan Zou, Ke Qiao, Chengyu Jin, Yijun Li, Meng Lu, Alex F. Chen, Sifeng Chen

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Background: Fine ambient particle matter (PM2.5) induces inflammatory lung injury; however, whether intratracheal administration of PM2.5 increases pulmonary polymorphonuclear leukocyte (PMN) infiltration, the mechanism of infiltration, and if these cells exacerbate PM2.5-induced lung injury are unknown. Methods: Using 32,704 subjects, the association between blood PMNs and ambient PM2.5 levels on the previous day was retrospectively analyzed. Neutropenia was achieved by injecting mice with PMN-specific antibodies. Inhibition of PMN infiltration was achieved by pretreating PMNs with soluble vascular cell adhesion molecule-1 (sVCAM-1). The effects of PMNs on PM2.5-induced lung injury and endothelial dysfunction were observed. Result: Short-term PM2.5 (> 75 μg/m3 air) exposure increased the PMN/white blood cell ratio and the PMN count in human peripheral blood observed during routine examination. A significant number of PM2.5-treated PMNs was able to bind sVCAM-1. In mice, intratracheally-instilled PM2.5 deposited in the alveolar space and endothelial cells, which caused significant lung edema, morphological disorder, increased permeability of the endothelial-alveolar epithelial barrier, and PMN infiltration with increased VCAM-1 expression. Depletion of circulatory PMNs inhibited these adverse effects. Replenishment of untreated PMNs, but not those pretreated with soluble VCAM-1, restored lung injury. In vitro, PM2.5 increased VCAM-1 expression and endothelial and epithelial monolayer permeability, and promoted PMN adhesion to, chemotaxis toward, and migration across these monolayers. PMNs, but not those pretreated with soluble VCAM-1, exacerbated these effects. Conclusion: VCAM-1-mediated PMN infiltration was essential for a detrimental cycle of PM2.5-induced inflammation and lung injury. Results suggest that drugs that inhibit PMN function might prevent acute deterioration of chronic pulmonary and cardiovascular diseases triggered by PM2.5.

Original languageEnglish
Pages (from-to)60-74
Number of pages15
JournalToxicology Letters
Volume302
DOIs
Publication statusPublished - Mar 1 2019
Externally publishedYes

Keywords

  • Fine ambient particle matter
  • Lung injury
  • Polymorphonuclear leukocyte
  • Vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Toxicology

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