Perspective: ambient air pollution: inflammatory response and effects on the lung's vasculature

Abstract

Particulates from air pollution are implicated in causing or exacerbating respiratory and systemic cardiovascular diseases and are thought to be among the leading causes of morbidity and mortality. However, the contribution of ambient particulate matter to diseases affecting the pulmonary circulation, the right heart, and especially pulmonary hypertension is much less documented. Our own work and that of other groups has demonstrated that prolonged exposure to antigens via the airways can cause severe pulmonary arterial remodeling. In addition, vascular changes have been well documented in a typical disease of the airways, asthma. These experimental and clinical findings link responses in the airways with responses in the lung's vasculature. It follows that particulate air pollution could cause, or exacerbate, diseases in the pulmonary circulation and associated pulmonary hypertension. This perspective details the literature for support of this concept. Data regarding the health effects of particulate matter from air pollution on the lung's vasculature, with emphasis on the lung's inflammatory responses to particulate matter deposition and pulmonary hypertension, are discussed. A deeper understanding of the health implications of exposure to ambient particulate matter will improve our knowledge of how to improve the management of lung diseases, including diseases of the pulmonary circulation. As man-made ambient particulate air pollution is typically linked to economic growth, a better understanding of the health effects of exposure to particulate air pollution is expected to integrate the global goal of achieving healthy living for all.

Keywords: airways; cardiovascular; particulate matter; pulmonary circulation; pulmonary hypertension; pulmonary immune responses.

Figure 1

Routes of transfer of particulate matter (PM) from the airways to peripheral organs and inflammatory response. PM effects in the heart and other organs involve dissemination of PM via blood vessels (red arrows) or drainage via the lymphatics (gray line) to the lymph node, followed by dissemination via blood vessels (red arrow). Translocated materials include: (a) the PM itself (nanoparticles), (b) components of disintegrated PM, (c) phagocytic immune cells that have phagocytosed PM and that migrate via the lymphatics to the lymph nodes, and (d) inflammatory mediators (e.g., cytokines) produced in the lungs in response to PM deposits.

Figure 2

Significant exacerbation of pulmonary arterial remodeling due to combined exposure to antigen and urban PM2.5 (particulate matter <2.5 μm in aerodynamic diameter). A, B, Arterial remodeling as average remodeling score per lung (A) and as percentage of severely remodeled arteries in the lungs (B); box plots with individual data points, n = 4–10. C, Numbers of eosinophils (i), neutrophils (ii), and CD11c+ cells (iii; note linear scale) in the bronchoalveolar lavage samples; bar graphs show means, standard error of the means (SEM), and individual data points (n = 6–10). D, E, Blood vessel muscularization. D, Representative histological sections from a phosphate-buffered-saline (PBS)-exposed mouse (i) and a PM-exposed mouse (ii) stained with anti–smooth muscle actin (dark; scale bars = 50 μm). E, Quantitative analysis of muscularization as percentage of blood vessels that were in each of the following categories: none (<30% of the circumference positive for smooth muscle actin staining), partial (30%–80% of the circumference positive), or full (>80% of the circumference positive); bar graphs show means, SEM, and individual data points (n = 4–5). In A–C, significant differences (P < 0.05, 2-tailed, unpaired Mann-Whitney test) relative to groups of mice exposed to saline (a) or ovalbumin (OVA; b) are indicated; ns: not significant. The study was performed in two independent experiments using C57BL/6 wild-type mice that were purchased from Jackson Labs and housed in specific pathogen-free conditions under the supervision of the Institutional Animal Care and Use Committee at New York University Medical Center as described.^, The mice were immunized by intraperitoneal injection with OVA complexed to alum and given intranasal challenges in a 50-μl volume per dose using the described schedule.^,, PM2.5 was collected in New York City by Dr. Gordon’s group, as described, and diluted in saline to a concentration of 0.5 mg/mL. The intranasal dose of OVA was 100 μg, and for the OVA-PM instillations, OVA and PM2.5 were mixed to achieve final concentrations of 100 and 25 μg per instillation, respectively. Bronchoalveolar lavage,^, arterial remodeling,^, and blood vessel muscularization were analyzed as published. The percentage of severely remodeled arteries was calculated as a fraction of arteries given the score 1.5 or 2 (severely thickened arterial wall with irregularity of wall thickening and cellular disorganization). In comparison, a score of 0 represented a normal artery, and a score of 1 was given for mild, circular thickening of the artery wall. A color version of this figure is available online.

Figure 3

Exposure to the combination of antigen (ovalbumin [OVA]) and urban ambient particulate matter (PM) causes increased pressures in the pulmonary circulation. Right ventricular systolic pressure (RVSP) is shown by notched box plots and circles showing individual data points (A) and by a bar graph showing the number of observations of RVSP less or greater than 26 mmHg (B). Data were pooled from two independent experiments; n = 4–10. The letter a indicates P < 0.05 compared to group of mice exposed to saline by 2-tailed, unpaired Mann-Whitney test (A) or by χ² test and 2-tailed Fisher’s exact test (B); ns: not significant.