EXPRESSION OF BETA-2-ADRENERGIC RECEPTOR MESSENGER-RNA IN PERIPHERAL LUNG IN ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

Previous studies have indicated an increased number of beta2-adrenergic receptors (beta2AR) on bronchial smooth muscle in fatal asthma. This study evaluates the utility of autopsy lung for studies of gene expression and examines the hypothesis that increased expression of beta2AR mRNA in peripheral lung underlies the increased receptor number reported in central airways in fatal asthma. Beta2AR mRNA levels have been quantitated using the ribonuclease protection assay on RNA from peripheral lung obtained both at autopsy and thoracotomy from subjects with normal lungs as well as subjects with asthma or chronic obstructive pulmonary disease (COPD). Glucocorticosteroid and serum induction of beta2AR mRNA in human epidermoid carcinoma A431 cells, which display a high abundance of beta2AR receptors, was also examined to provide aliquots of RNA containing relatively high levels of beta2AR mRNA for use as positive controls and internal standards. In A431 cells maintained after confluence in serum-free media for 72 h, maximal beta2AR mRNA levels in response to 10% fetal bovine serum were 85% of maximal levels following serum plus 10 muM dexamethasone. Both autopsy and resected lung yielded undegraded RNA with a similar relative abundance of beta2AR mRNA. Although geometric mean beta2AR mRNA levels were similar in all three patient groups, relatively high levels were observed in resected lung in a subpopulation of subjects with mild or moderate asthma but not in autopsy lung from subjects with severe asthma. High levels of beta2AR mRNA, presumably reflecting lung growth or asthma, were demonstrated in peripheral lung of a 4-yr-old child with asthma. These data show that selected autopsy lung is suitable for studies of gene expression and suggest that beta2AR mRNA expression is increased in some subjects with asthma but not with COPD. Future studies should directly compare beta2AR mRNA levels in bronchial smooth muscle with receptor number.