Aerosolized Hyaluronan Reduces Airspace Enlargement and Elastic Fiber Injury in a Mouse Model of Cigarette Smoke-Induced Pulmonary Emphysema
Jerome Cantor, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences
J. Cerreta, M. Ochoa, S. Ma, T. Chow, G. Grunig, and G. Turino, St. John’s University, and St. Lukes - Roosevelt Hospital Center, New York, NY
The overall objective of this study was to determine if an aerosolized solution of hyaluronan (HA) could prevent pulmonary airspace enlargement in mice exposed to tobacco smoke for an extended period of time. Compared to earlier studies from this laboratory demonstrating that aerosolized HA significantly reduces airspace enlargement in an elastase model of emphysema, the smoking model presents a more stringent test of HA against a chronic form of lung injury that shares at least some of the features of the human disease process. Mice (DBA/2J) were divided into 2 groups, one receiving treatment with aerosolized HA (0.1% solution in water) for 1 hour and the other receiving aerosolized water alone over the same time period. Both groups were then exposed to cigarette smoke for 3 hrs. This routine was repeated 5 days/week for a period of 6 months. Both lung tissues and lavage fluid were examined at monthly intervals. All the mice appeared active and healthy throughout the study and tolerated the aerosol and smoke exposure. Histological evaluation of the smoke-exposed lungs from both groups showed rapid development of emphysematous lesions. Airspace enlargement was relatively uniform throughout the lung, indicative of a panacinar disease process. Lavaged cells from both groups consisted almost entirely of macrophages with abundant carbon granules. Treatment with HA significantly reduced airspace enlargement over the 6-month course of the experiment (p<0.001). The level of elastin-specific amino acids, desmosine and isodesmosine, was also lower in lavage fluid from animals exposed to HA (p<0.05), consistent with reduced breakdown of elastic fibers. Light microscopic examination of HA-treated lungs did not reveal any pulmonary inflammation beyond that caused by exposure to cigarette smoke. The results further suggest the potential efficacy of aerosolized HA as a treatment for pulmonary emphysema.