Expression of beta 2-adrenergic receptor mRNA in peripheral lung in asthma and chronic obstructive pulmonary disease.

Abstract

Previous studies have indicated an increased number of beta 2-adrenergic receptors (beta 2AR) 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 beta 2 AR mRNA in peripheral lung underlies the increased receptor number reported in central airways in fatal asthma. beta 2AR 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 beta 2AR mRNA in human epidermoid carcinoma A431 cells, which display a high abundance of beta 2AR receptors, was also examined to provide aliquots of RNA containing relatively high levels of beta 2AR mRNA for use as positive controls and internal standards. In A431 cells maintained after confluence in serum-free media for 72 h, maximal beta 2AR mRNA levels in response to 10% fetal bovine serum were 85% of maximal levels following serum plus 10 microM dexamethasone. Both autopsy and resected lung yielded undegraded RNA with a similar relative abundance of beta 2AR mRNA. Although geometric mean beta 2AR 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 beta 2AR mRNA, presumably reflecting lung growth or asthma, were demonstrated in peripheral lung of a 4-yr-old child with asthma.(ABSTRACT TRUNCATED AT 250 WORDS)