The Impact of Environmental Pollutants on Barrier Dysfunction in Respiratory Disease

Abstract

Respiratory epithelial cells form a selective barrier between the outside environment and underlying tissues. Epithelial cells are polarized and form specialized cell-cell junctions, known as the apical junctional complex (AJC). Assembly and disassembly of the AJC regulates epithelial morphogenesis and remodeling processes. The AJC consists of tight and adherens junctions, functions as a barrier and boundary, and plays a role in signal transduction. Endothelial junction proteins play important roles in tissue integrity and vascular permeability, leukocyte extravasation, and angiogenesis. Air pollutants such as particulate matter, ozone, and biologic contaminants penetrate deep into the airways, reaching the bronchioles and alveoli before entering the bloodstream to trigger airway inflammation. Pollutants accumulating in the lungs exacerbate the symptoms of respiratory diseases, including asthma and chronic obstructive lung disease. Biological contaminants include bacteria, viruses, animal dander and cat saliva, house dust mites, cockroaches, and pollen. Allergic inflammation develops in tissues such as the lung and skin with large epithelial surface areas exposed to the environment. Barrier dysfunction in the lung allows allergens and environmental pollutants to activate the epithelium and produce cytokines that promote the induction and development of immune responses. In this article, we review the impact of environmental pollutants on the cell barrier in respiratory diseases.

Keywords: Air pollution; asthma; barrier; chronic obstructive pulmonary disease; environmental pollutants; epithelium; house dust mites; ozone; particulate matter.

Fig. 1. Structure of the AJC. The AJC consisting of the TJ and AJ resides at the interface between the apical and basolateral membrane.

AJC, apical junctional complex; TJ, tight junction; AJ, adherens junction.

Fig. 2. (A) Plasma CLDN4 level between stable and exacerbated states of asthmatic subjects and control subjects. (B) Plasma CLDN5 levels in patients with COPD and control subjects, and in patients with stable or exacerbated COPD.

COPD, chronic obstructive pulmonary disease; CLDN, claudin. ^*P < 0.05, compare to control; ^†P < 0.05, stable vs. exacerbated (modified from references5663).