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Bronchial Mast Cells Are the Dominating LTC₄S-Expressing Cells in Aspirin-Tolerant Asthma

Institute of Oral Biology, University of Oslo, Oslo; Department of Circulation and Medical Imaging, Medical Faculty NTNU, Trondheim; and Department of Lung Medicine, University Hospital of Trondheim, Trondheim, Norway

Address correspondence to: Dr. Trond S. Halstensen, Institute of Oral Biology, University of Oslo, PB 1052, Blindern, 0316 Oslo, Norway. E-mail: thalsten{at}odont.uio.no

The increased bronchial production of leukotriene C₄ (LTC₄) in asthma is assumed to derive from infiltrating eosinophils expressing LTC₄-synthase (LTC₄S). Multicolor immunohistofluorescence examination of bronchial cryosections from 30 treated, untreated, or bronchial antigen–provoked aspirin-tolerant individuals with asthma and nine control subjects revealed that the dominating LTC₄S-expressing cells were mast cells (> 80%), and not eosinophils. Whereas 95% of the mast cells expressed high levels of LTC₄S, only 8–27% of the eosinophils expressed low levels. Image analysis revealed a significantly higher LTC₄S expression levels in mast cells than in eosinophils. The bronchial mRNA levels for LTC₄S did not correlate with the densities of LTC₄S-positive eosinophils or mast cells. Treated individuals with asthma with more than 12% reversibility had significantly higher density of LTC₄S-positive mast cells than those with less reversibility, and it correlated significantly with reduction in lung function (FEV₁-predicted), both before and after salbutamol inhalation. Thus, mucosal mast cells, and not eosinophils, were the dominating LTC₄S-containing cells in both untreated and treated aspirin-tolerant asthma. The density of LTC₄S-positive mast cells correlated, moreover, with both the reduction in lung function and the degree of reversibility in treated asthma.

Abbreviations: diffraction interface contrast, DIC • 5-lipo-oxygenase activating protein, FLAP • glycol methacrylate, GMA • horseradish peroxidase, HRP • inhaled corticosteroid, ICS • interleukin, IL • leukotriene, LT • leukotriene C₄-synthase, LTC₄S • microsomal glutation S-transferase, mGST-II • phosphate-buffered saline, PBS • prostaglandin, PG • periodate-lysine-paraformaldehyd, PLP • reverse transcriptase–polymerase chain reaction, RT-PCR