Elevated expression of adenosine A1 receptor in bronchial biopsy specimens from asthmatic subjects.
Asthmatics, unlike healthy subjects, experience bronchoconstriction in response to inhaled adenosine, and extracellular adenosine concentrations are elevated in the bronchoalveolar lavage fluid and exhaled breath condensate of asthmatic subjects. However, little is known about the location and expression of adenosine receptors in asthmatic airways. The aim of the present study was to investigate the distribution of adenosine A(1) receptors in bronchial biopsy specimens from mildly asthmatic steroid-naïve subjects and then compare the degree of expression with that of healthy subjects. Biopsy sections were immunostained using an adenosine A(1) receptor antibody, the selectivity of which was validated in specific experiments. Image analysis was then performed in order to determine differences in immunostaining intensity. Immunostaining of biopsy sections from the asthmatic subjects revealed strong expression of the A(1) receptor, located predominantly in the bronchial epithelium and bronchial smooth muscle. In comparison, very weak immunostaining was observed in biopsy specimens obtained from healthy subjects. Image analysis revealed that the intensity of positive staining of the asthmatic bronchial epithelium and smooth muscle regions was significantly greater than that observed for the healthy epithelium and smooth muscle. In conclusion, the sensitivity of asthmatics to inhaled adenosine coupled with increased adenosine A(1) receptor expression implies that these receptors play a role in the pathophysiology of this disease.
Brown
R A
RA
Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, London, SE1 1UL, UK.
Clarke
G W
GW
Ledbetter
C L
CL
Hurle
M J
MJ
Denyer
J C
JC
Simcock
D E
DE
Coote
J E
JE
Savage
T J
TJ
Murdoch
R D
RD
Page
C P
CP
Spina
D
D
O'Connor
B J
BJ
D000241:Adenosine / Q000008:administration & dosage; D000280:Administration, Inhalation; D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D001980:Bronchi / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000175:diagnosis*; D001985:Bronchial Provocation Tests; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011379:Prognosis; D043682:Receptor, Adenosine A1 / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D012129:Respiratory Function Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015854:Up-Regulation
D015415:Biomarkers; D043682:Receptor, Adenosine A1; D000241:Adenosine