© 2005 American Thoracic Society
Chymase-positive Mast CellsA Double-Edged Sword in Asthma?To the Editor:The recent article by Dr. Balzar and colleagues suggests that chymase-positive mast cells in small airways may be protective for lung function in severe asthma on the basis of a positive correlation between the number of mast cells containing chymase in the small airway outer wall and FEV1 values (1). However, in designing their morphometric analysis, the authors have considered only two small airway regions: the small inner wall, i.e., the area from the subepithelial basement membrane to the inner edge of smooth muscle, and the small airway outer wall, i.e., the area from the outer edge of the smooth muscle layer to the alveolar attachments. As a consequence, the smooth muscle layer was not examined, although recent data have highlighted the importance of its infiltration by mast cells in asthma (2, 3). In this connection, there is evidence from both in vitro and in vivo experiments that human airway smooth muscle cells are able to attract mast cells of both subtypes, MCT and MCTC, by secreting chemoattracting factors, such as transforming growth factor (TGF)-ß1 and stem cell factor (SCF) (4). Moreover, the number of chymase-positive mast cells in the smooth muscle layer of small airways correlates with peripheral obstruction detected by CT scan in smokers (5). Therefore, a higher concentration of chymase-positive mast cells in the small airway outer wall may simply reflect a lower infiltration of the smooth muscle layer and vice versa. As a consequence, the protective effect of distal lung mast cells may be ascribed to a lower concentration, and thus to a less deleterious effect of mast cells located in the airway smooth muscle. The mechanism providing the protective role of mast cells suggested by the authors deals with the interesting hypothesis of a different mast cell phenotype containing chymase and displaying a positive effect on remodelling unlike that of tryptase. Again, it should be kept in mind that mast cells of MCTC phenotype, that contain chymase, have even higher amounts of tryptase than MCT mast cells that contain tryptase only (6). Taking into account these established data on protease content, it is noteworthy that in the series of Balzar and coworkers the number of MCTC and the MCTC/MCT ratio were higher in patients with severe asthma. Thus, whereas the observation by Balzar and coworkers is undoubtedly of value, assigning a protective role to chymase-positive mast cells in asthma first requires a comprehensive analysis of mast cell infiltration in distal airways of asthmatic patients.
INSERM E356, Université Victor Segalen, Bordeaux, France FOOTNOTES Conflict of Interest Statement: J.M.T.d.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; P.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; R.M. 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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