Epithelial Barrier Dysfunction
Recent research has positioned airway epithelial cells at the center of mucosal immune responses, because they sense and respond to inhaled allergens, particles and viruses and influence both innate and adaptive immunity. In addition to producing chemokines and cytokines that recruit and activate their target cells, epithelial cells form a physical barrier to the outside world. The epithelial barrier includes apical junctional complexes (AJC) consisting of tight and adherens junctions between neighboring cells. Emerging evidence indicates that epithelial AJC dysfunction is associated with asthma, but mechanisms involved in this process are poorly understood.
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LPA and Autotaxin: Novel Regulators of Lymphocyte Trafficking and Airway Inflammation
Lysophosphatidic acid (LPA) is a pleiotropic lipid molecule with potent effects on cell growth and motility. Major progress has been made in recent years in deciphering the mechanisms of LPA generation and how it acts on target cells. Most research to-date has been conducted in other disciplines, but emerging data indicate that LPA has an important role to play in immunity. A key discovery was that autotaxin (ATX), an enzyme previously implicated in cancer cell motility, generates extracellular LPA from the precursor lysophosphatidylcholine (LPC).
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The Leaky Lung Test
There are no good assays of outside/in airway epithelial permeability in clinical use, which has slowed research in this area. Current studies rely on bronchoscopy with bronchial biopsy and brushings to document structural and functional changes in airway epithelial junctions, but this is not practical for large-scale studies and introduces artifacts of in vitro cell propagation. A more specific non-invasive assay of outside/in airway permeability would be useful in clinical asthma research, and allow us to ask specific questions in a translational manner.
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