TY - JOUR
T1 - VCAM-1-mediated neutrophil infiltration exacerbates ambient fine particle-induced lung injury
AU - Cui, Anfeng
AU - Xiang, Meng
AU - Xu, Ming
AU - Lu, Peng
AU - Wang, Shun
AU - Zou, Yajuan
AU - Qiao, Ke
AU - Jin, Chengyu
AU - Li, Yijun
AU - Lu, Meng
AU - Chen, Alex F.
AU - Chen, Sifeng
N1 - Funding Information:
This study was supported by General Program (grant number 81470260 to M. Xiang), Great Research Plan Program (grant number 91539120 to S. Chen), and great International Cooperation and Exchange project (grant number 81220108002 to S. Chen) of the National Natural Science Foundation of China, and the National Key R&D Program of China (grant number 2016YFC1305101 to S. Chen).
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
KW - Fine ambient particle matter
KW - Lung injury
KW - Polymorphonuclear leukocyte
KW - Vascular cell adhesion molecule-1
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U2 - 10.1016/j.toxlet.2018.11.002
DO - 10.1016/j.toxlet.2018.11.002
M3 - Article
C2 - 30447258
AN - SCOPUS:85059057067
SN - 0378-4274
VL - 302
SP - 60
EP - 74
JO - Toxicology Letters
JF - Toxicology Letters
ER -
