Diesel Exhaust Particles Enhance Lung Injury Related to Bacterial Endotoxin through Expression of Proinflammatory Cytokines, Chemokines, and Intercellular Adhesion Molecule-1

Abstract

Epidemiologic studies demonstrate acute and serious adverse effects of particulate air pollution on respiratory health, especially in people who are susceptible to bacterial infection. However, the underlying mechanism remains to be elucidated. To provide experimental evidence for the epidemiologic data, we determined the effects of diesel exhaust particles (DEP), major participants in particulate pollutants, on lung injury related to bacterial endotoxin in mice. Intratracheal instillation of DEPs synergistically enhanced lung injury related to endotoxin from gram-negative bacteria, which was characterized by neutrophil sequestration, interstitial edema, and alveolar hemorrhage. In the presence of endotoxin, DEPs further activated the nuclear translocation of p65 subunit of nuclear factor-kappaB (NF-kappaB) in the lung and increased the lung expression of intercellular adhesion molecule-1, interleukin-1beta, macrophage chemoattractant protein-1, keratinocyte chemoattractant (KC), macrophage inflammatory protein-1alpha, and Toll-like receptors. DEPs given alone increased the lung expression of Toll-like receptor 4 and the nuclear localization of p50 subunit of NF-kappaB. The combined exposure to DEPs and endotoxin decreased nuclear localization of CCAAT/enhancer binding protein beta. These results provide the first experimental evidence that DEPs enhance neutrophilic lung inflammation related to bacterial endotoxin. The enhancement is mediated by the induction of proinflammatory molecules, likely through the expression of Toll-like receptors and the activation of p65-containing dimer(s) of NF-kappaB, such as p65/p50.

Promoting effects of nanoparticles/materials on sensitive lung inflammatory diseases

“…In addition, one intriguing aspect of the epidemiologic data is that health effects of PM 2.5 are primarily seen in subjects with predisposing factors, including pneumonia, asthma, chronic obstructive pulmonary disease, compromised immune systems, and age over 65 years old [3]. Consistent with the epidemiological studies, we have experimentally demonstrated that diesel exhaust particles (DEP), major contributors to environmental PM 2.5 in urban areas, exhibit respiratory toxicity with or without predisposing factors in vivo [4][5][6][7][8][9][10].…”

“…In addition, LPS is a significant constituent of many air pollutant particles and has accordingly been implicated in the adverse effects of PM [33]. In accordance with the close links among LPS, lung inflammation (injury), and PM, we have previously shown that intratracheal administration of DEP and their components facilitates lung inflammation induced by LPS [8,34] and subsequent systemic inflammation with coagulatory disturbance [9].…”

Diesel Exhaust Particles Synergistically Enhance Lung Injury and Oxidative Stress Induced by Bacterial Endotoxin

“…1C), tumor necrosis factor (TNF)-α, keratinocyte chemoattractant (KC), macrophage chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1α ( Fig. 1D) in the lung have paralleled the lung injury and neutrophilic inflammation by DEP and LPS [21]. The accumulation of leukocytes within the lung in inflammation is generally dependent on alterations in leukocyte rigidity, the coordinated expression of proinflammatory cytokines, and the establishment of chemotactic gradients via the local generation of chemotactic factors [22].…”

“…1A) and neutrophil sequestration (Fig. 1B) [21]. The local expression of proinflammatory cytokines such as interleukin-(IL)-1β ( Fig.…”

Effect of ultrafine zinc oxide (ZnO) nanoparticles on induction of oral tolerance in mice

“…Furthermore, the difference in toxicity between ZnO and DEP might also explain the difference in the effect on oral tolerance since the toxic effect of chemical compounds might be related to the damage of the mucosal immune system, resulting in the modulation of induction of oral tolerance. DEP has been shown to contain a number of organic toxic compounds that enhance lung injury via the production of proinflammatory cytokine and chemokines (Takano et al, 2002). In contrast, especially fine ZnO has been utilized as a safe chemical (Scientific Committee on Cosmetic Products and Non-food Products, 2003).…”