Modulation of Airway Inflammation By Surfactant Proteins

Duke University, Durham NC

Investigators

Abstract

DESCRIPTION (provided by applicant): Asthma is a chronic disorder of the airways characterized by reversible airflow obstruction, persistent airway hyperreactivty, airway remodeling, and inflammation. An estimated 15 million Americans are affected by asthma and the morbidity and mortality associated with it are increasing. While surfactant has traditionally been view as a surface active agent, its proteins SP-A and SP-D have recently been found to modulate immunity in the alveolar compartment. In this study, SP-A and SP-D knockout mice will be utilized to evaluate the effects of surfactant proteins A and D on modulating the airway hyperreactivity and the inflammatory response in mice exposed to aerosolized endotoxin. Airway resistance will be measured by the airway pressure time index in knockout and wild type mice exposed to aerosolized LPS. Bronchoalveolar lavage fluid will be sampled for cytokines and lung tissue will be harvested for RNA extraction and histological analysis. Cytokine and chemokine message will be assayed for by ribonuclease protection assay and additional RNA will be sent for microarray studies. It is hoped that array analysis may help elucidate the mechanism by which surfactant proteins affect cellular processes. If SP-A and SP-D do modulate airway hyperreactivity and inflammation then rescue studies with recombinant surfactant proteins will be performed.