IL-13 and Pulmonary Smooth Muscle Biology

摘要

Smooth muscle cells are important players in several chronic diseases of the lungs. Airway smooth muscle dysfunction has been shown to be associated with airway constriction and hyperreactiv-ity in asthma, and pulmonary arterial muscularization is one of the main histologic signs in pulmonary arterial hypertension (PAH). Our studies found serendipitously that sensitized C57BL/6 mice exposed to antigen intermittently for a prolonged period of time developed severe pulmonary arterial remodeling with smooth muscle cell hyperplasia. Interleukin (IL)-4, IL-13, and CD4+ T lymphocytes were necessary for the development of severe pulmonary arterial muscularization, but exposure with recombi-nant IL-13 was not sufficient. Right ventricular systolic pressures after acute exposure to hypoxia were increased in mice that had severely muscularized pulmonary arteries, but were not elevated under normoxic conditions. These findings support the clinical observations in pediatric patients and in companion animals that muscularization represents one of several injurious events to the pulmonary artery that together may contribute to PAH. Our studies are important for the understanding of the pathobiology of the lung because they suggest the hypothesis that not simply hyperplasia, but dysfunction of the smooth muscle cells leads to increased contraction. Furthermore, it is intriguing that IL-13 can mediate different types of conditions: airway hyperreactivity by a process that can be entirely elicited by IL-13, and pulmonary arterial muscularization via a cooperative mechanism between IL-13 and components of the immune and inflammatory response.