Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema

Abstract

Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c+ lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.DOI: http://dx.doi.org/10.7554/eLife.09623.001

Validating Metal‐Organic Framework Nanoparticles for Their Nanosafety in Diverse Biomedical Applications

“…Nanoparticle‐mediated drug delivery into the lung via inhalation represents a novel concept for treatment of lung diseases . It is hampered, however, by the fact that the applied nanocarriers have detrimental side effects for the lung which may either result from acute inflammation and cytotoxicity or upon their accumulation in lung tissue over time causing chronic lung inflammation as shown previously . The here studied MOFs represent a novel type of biodegradable nanomaterial which may possibly overcome these limitations.…”

Cigarette smoke–induced reduction of C1q promotes emphysema

“…C1q deficiency in human APCs skews Treg and Th17 cell induction. We and others have previously shown that the NLRP3 inflammasome and associated cytokines are required for the inflammation induced by nano-sized carbon black particle inhalation (3). Therefore, we next examined whether activation of the NLRP3 inflammasome could play a direct role in the loss of C1q expression in APCs.…”

“…Exposure to chronic cigarette smoke and the particulate matter derived from the incomplete combustion of tobacco (e.g., nano-sized carbon black) can cause irreversible destruction of the lung parenchyma, termed emphysema, a form of chronic obstructive pulmonary disease (COPD; refs. [1][2][3][4]. The pathogenesis of pulmonary emphysema, an endotype of smoke-induced inflammatory lung diseases that is associated with high morbidity and affects a subset of smokers, remains incompletely understood.…”

Translocation of Endogenous Danger Signal HMGB1 From Nucleus to Membrane Microvesicles in Macrophages

“…The danger signals from damaged or dead cells guide leukocytes to the sites of sterile inflammation, and contribute to many pathologic conditions or human diseases (Chen and Nunez, ; Shen et al, ). Tobacco smoking is a major cause of sterile inflammation (You et al, ) in various inflammatory diseases in humans (Johannsen et al, ; Yuan et al, ; Perricone et al, ). As a DAMP molecule, HMGB1 is elevated in the blood in humans and animals that are exposed to tobacco smoke (Saiwichai et al, ; Krakowiak et al, ).…”