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Toxicol Lett. 2019 Mar 1;302:60-74. doi: 10.1016/j.toxlet.2018.11.002. Epub 2018 Nov 15.

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

Author information

1
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, 130 Dongan Road, Building 7, Room 214, Shanghai, 200032, PR China.
2
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, 130 Dongan Road, Building 7, Room 214, Shanghai, 200032, PR China. Electronic address: xmeng@shmu.edu.cn.
3
Instrumental Analysis Center, Shanghai Jiao Tong University, 800 Dongchuan Road, Building 3, Room 302, Shanghai, 200240, PR China.
4
Key Laboratory of Medical Molecular Virology, Ministry of Education and Public Health, School of Basic Medical Sciences, Fudan University, 131 Dongan Road, Building 1, Room 361, Shanghai, 200032, PR China.
5
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, 130 Dongan Road, Building 7, Room 214, Shanghai, 200032, PR China. Electronic address: chen1216@fudan.edu.cn.

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.

KEYWORDS:

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

PMID:
30447258
DOI:
10.1016/j.toxlet.2018.11.002
[Indexed for MEDLINE]

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