© 2005 American Thoracic Society
Chymase-positive Mast CellsA Double-Edged Sword in Asthma?From the Authors:We appreciate the opportunity to further address issues regarding the role of mast cells in asthma as raised in response to our recent article (1). Dr. Tunon-de-Lara and colleagues suggest that tryptase activity from mast cells specifically within the airway smooth muscle may significantly affect lung function of subjects with asthma and that our observed protective effect of chymase-positive mast cells in small airway outer wall/alveolar attachments may actually be due to fewer chymase-positive mast cells within the small airway smooth muscle area. They hypothesize that potentially lower numbers of chymase-positive mast cells (which they suggest contain more tryptase than chymase-negative mast cells) within smooth muscle could contribute to better lung function due to the diminished presence/effect of tryptase within smooth muscle. Although we are not able to completely rule out these possibilities, we believe that several lines of evidence makes them less likely. First, we are not able to confirm the work of others that found differences in mast cell numbers in smooth muscle from airways of subjects with asthma versus control subjects. Our studies of large airways indicate that there are little or no differences between the number of mast cells in various large airway regions, with no relationship of location or mast cell phenotype to lung function (2). We did not evaluate small airway smooth muscle because the amount of smooth muscle area available for analysis in the small airways is relatively small, increasing the likelihood for error. Second, there are a few subjects in our study in whom some mast cells are positive only for chymase, without detectable tryptase. This might argue against there being more tryptase in chymase-positive than in chymase-negative mast cells. Third, the concept that mast cells compartmentalize to the smooth muscle, where tryptase may be more likely to have negative local effects, should be viewed cautiously. Tryptase, unlike chymase, has a high diffusion capability and is readily detectable in bronchoalveolar lavage and serum from subjects with asthma. Therefore, a more feasible scenario for tryptase activity in vivo is over a spatial gradient rather than in distinct compartments. Consequently, a tryptase-regulated environment within smooth muscle is not likely to be exclusively induced by smooth muscle mast cells or, for that matter, mast cells from any particular tissue region. These gradient effects are likely to produce a similar environment in both the submucosa and smooth muscle (3–5). If intracellular mast cell tryptase is related to lung function in asthma, we should be able to detect such a relationship in small airway regions, even without definitive smooth muscle analysis. However, there was no evidence for either a positive or negative relationship between the number of tryptase-positive mast cells in large or small airways and lung function in asthma (1). While these studies do not definitively rule in or out a role for tryptase in severe asthma, the relationship with chymase-positive cells is strong and consistent. Certainly, more studies are necessary to fully characterize the functional differences between mast cell phenotypes in tissue and their role in diseases such as asthma.
National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colorado FOOTNOTES Conflict of Interest Statement: S.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; S.E.W. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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