Ultrafine Carbon Black Particles Enhance Respiratory Syncytial Virus-Induced Airway Reactivity, Pulmonary Inflammation, and Chemokine Expression

Abstract

Exposure to particulate matter (PM) may exacerbate preexisting respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), bronchitis, and pneumonia. However, few experimental studies have addressed the effects of PM on lower respiratory tract (LRT) viral infection. Respiratory syncytial virus (RSV) is a major etiological agent for LRT infections in infants, the elderly, and the immunocompromised and may lead to chronic wheezing and the development of asthma in children. In this study, we examined the effects of carbon black (CB) on RSV-induced pulmonary inflammation, chemokine and cytokine expression, and airway hyperresponsiveness in a mouse model of RSV. Female BALB/c mice were instilled via the trachea (i.t.) with 1 x 106 plaque forming units (pfu) RSV or with uninfected culture media. On day 3 of infection, mice were i.t. instilled with either 40 micro g ultrafine CB particles or with saline. End points were examined on days 4, 5, 7, and 14 of RSV infection. Viral titer and clearance in the lung were unaffected by CB exposure. Neutrophil numbers were elevated on days 4 and 7, and lymphocyte numbers were higher on days 4 and 14 of infection in CB-exposed, RSV-infected mice. CB exposure also enhanced RSV-induced airway hyperresponsiveness to methacholine, bronchoalveolar lavage (BAL) total protein, and virus-associated chemokines monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1 alpha), and regulated upon activation, normal T cell expressed and secreted (RANTES). MIP-1 alpha mRNA expression was increased in the alveolar epithelium, where ultrafine particles deposit in the lung. These data demonstrate a synergistic effect of ultrafine CB particles on RSV infection, and suggest a potential mechanism for increased respiratory infections in human populations after PM exposure.

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function

“…In terms of inflammation, our findings partially agree with those of the one previous study which has considered the effects of PM exposure on existing respiratory viral‐induced disease 19 . Lambert et al.…”

“…Data on the effects of acute exposure to DE 18 or carbon black particles 17 , 19 on existing viral infection are also sparse. Such a scenario is consistent with exposure of an individual with an established respiratory viral infection to high levels of pollution on a bad smog day, while walking next to a busy road, working in a polluted environment or while travelling through a poorly ventilated traffic tunnel 10 , 20 .…”

“…Unfortunately, direct evidence for the impact of DEP specifically on existing respiratory viral‐induced disease is lacking. One study modelling this situation 19 . found that instilling mice with ultrafine carbon black particles 3 days after inoculation with respiratory syncytial virus (RSV) caused no change in lung viral titre, but increased neutrophils, lymphocytes, bronchoalveolar lavage (BAL) protein, virus‐associated chemokines and responsiveness to methacholine 19 .…”

“…One study modelling this situation 19 . found that instilling mice with ultrafine carbon black particles 3 days after inoculation with respiratory syncytial virus (RSV) caused no change in lung viral titre, but increased neutrophils, lymphocytes, bronchoalveolar lavage (BAL) protein, virus‐associated chemokines and responsiveness to methacholine 19 . However, although RSV is a potentially significant human pathogen, it typically produces a mild response in mice.…”

Síntomas respiratorios asociados a la exposición a contaminación del aire en cinco localidades de Bogotá, D.C., 2008-2011. Una cohorte dinámica

“…Según los datos reportados por las autoridades ambientales y los límites excedidos con respecto a la norma establecida en la Resolución 610 de 2010, el principal contaminante en Bogotá es el material en partículas, el cual tiene efectos directos sobre el aparato respiratorio e interactúa con los virus respiratorios, potenciando sus efectos (11). Según la Organización Mundial de la Salud, Bogotá es una de las ciudades de Latinoamérica más contaminadas con material en partículas de menos de 10 µm (PM 10 ) y 2,5 µm (PM 2,5 ), y los promedios anuales no cumplen con las recomendaciones para la protección de la población (PM 10 =48 µg/ m 3 , valor de referencia 20 µg/m 3 , y PM 2,5 =27 µg/ m 3 , valor de referencia 10 µg/m 3 ) (12).…”