ADAM33 expression in asthmatic airways and human embryonic lungs.
BACKGROUND
Polymorphic variation in ADAM33 (A Disintegrin And Metalloprotease) is strongly associated with asthma and bronchial hyperresponsiveness in different populations.


OBJECTIVE
To study the role of ADAM33 in asthma, we investigated its expression in normal, asthmatic, and embryonic airways using reverse transcriptase-quantitative polymerase chain reaction and immunochemistry.


RESULTS
Several ADAM33 mRNA splice variants were detected in bronchial biopsies and embryonic lung; however, the beta-isoform and variants encoding the metalloprotease domain were rare transcripts. Western blotting of bronchial biopsies confirmed the presence of multiple isoforms of ADAM33, which had molecular weights of 22, 37, 55, and 65 kD. Immunohistochemistry and laser confocal microscopy of adult bronchial biopsies showed that alpha-smooth muscle actin and ADAM33 immunoreactivity were mostly colocalized to smooth muscle and isolated cells in the submucosa. There was no significant difference in ADAM33 mRNA amplicons or protein in subjects with asthma compared with control subjects. In developing lung, ADAM33 was found around bronchial tubes; however, immunoreactivity was more widely distributed than alpha-smooth muscle actin within undifferentiated mesenchyme; on Western blots, an additional 25-kD ADAM33 variant was detected.


CONCLUSIONS
Several ADAM33 protein isoforms occur in adult bronchial smooth muscle and in human embryonic bronchi and surrounding mesenchyme, strongly suggesting its importance in smooth muscle development and/or function, which could explain its genetic association with bronchial hyperresponsiveness. The occurrence of ADAM33 in embryonic mesenchymal cells suggests that it may be involved in airway wall "modeling" that contributes to the early life origins of asthma.
Haitchi
Hans Michael
HM
Roger Brooke Laboratories, Division of Infection, Inflammation, and Repair, and Human Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital, United Kingdom. h.m.haitchi@soton.ac.uk
Powell
Robert M
RM
Shaw
Timothy J
TJ
Howarth
Peter H
PH
Wilson
Susan J
SJ
Wilson
David I
DI
Holgate
Stephen T
ST
Davies
Donna E
DE
D051722:ADAM Proteins; D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001980:Bronchi / Q000378:metabolism*; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008875:Middle Aged
D051722:ADAM Proteins; C450441:ADAM33 protein, human; D008666:Metalloendopeptidases