Enhanced expression of cyclo-oxygenase isoenzyme 2 (COX-2) in asthmatic airways and its cellular distribution in aspirin-sensitive asthma.
BACKGROUND
There are two isoforms of cyclo-oxygenase (COX), namely COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and in blood platelets. The metabolites derived from COX-1 are probably involved in cellular housekeeping functions. COX-2 is expressed only following cellular activation by inflammatory stimuli and is thought to be involved in inflammation.


METHODS
The expression of COX-1 and COX-2 isoenzymes has been studied in the bronchial mucosa of 10 normal and 18 asthmatic subjects, 11 of whom had aspirin-sensitive asthma (ASA) and seven had non-aspirin-sensitive asthma (NASA) RESULTS: There was a significant fourfold and 14-fold increase, respectively, in the epithelial and submucosal cellular expression of COX-2, but not of COX-1, in asthmatic patients. There was no significant difference in the total number of cells staining for either COX-1 or COX-2 between subjects with ASA and NASA, but the number and percentage of mast cells that expressed COX-2 was significantly increased sixfold and twofold, respectively, in individuals with ASA. There was a mean fourfold increase in the percentage of COX-2 expressing cells that were mast cells in subjects with ASA and the number of eosinophils expressing COX-2 was increased 2.5-fold in these subjects.


CONCLUSIONS
COX-2-derived metabolites may play an essential part in the inflammatory processes present in asthmatic airways and development of drugs targeted at this isoenzyme may have therapeutic potential in the treatment of asthma. Mast cells and eosinophils may also have a central role in the pathology of aspirin-sensitive asthma.
Sousa
A r
Ar
Department of Allergy and Respiratory Medicine, UMDS, Guy's Hospital, London, UK.
Pfister
R
R
Christie
P E
PE
Lane
S J
SJ
Nasser
S M
SM
Schmitz-Schumann
M
M
Lee
T H
TH
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D001980:Bronchi / Q000201:enzymology*; D002452:Cell Count; D004804:Eosinophils / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000201:enzymology / Q000473:pathology; D008875:Middle Aged; D009092:Mucous Membrane / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000378:metabolism*; D018709:Statistics, Nonparametric
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin