Lung mast cells are stereotypically divided into connective tissue (MC TC ) and mucosal (MC T ) mast cells. This study tests the hypothesis that each of these subtypes can be divided further into site-specific populations created by the microenvironment within each anatomical lung compartment. Methods: Surgical resections and bronchial and transbronchial biopsies from non-smoking individuals were obtained to study mast cells under non-inflamed conditions. Morphometric and molecular

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... cs of mast cell populations were investigated in multiple lung structures by immunohistochemistry and electron microscopy. Results: MC T and MC TC coexisted in all compartments, with MC T being the prevailing type in bronchi, bronchioles and the alveolar parenchyma and MC TC being more abundant in pulmonary vessels and the pleura. Each of the MC TC and MC T phenotypes could be further differentiated into site-specific populations. MC TC were significantly larger in pulmonary vessels than in small airway walls, while the reverse was observed for MC T . Within each MC TC and MC T population there were also distinct sitespecific expression patterns of the IgE receptor, interleukin-9 receptor, renin, histidine decarboxylase, vascular endothelial growth factor, fibroblast growth factor, 5-lipoxygenase and leukotriene C4 synthase (eg, bronchial MC T consistently expressed more histidine decarboxylase than alveolar MC T ). Renin content was high in vascular MC TC but markedly lower in MC TC in other compartments. For both MC TC and MC T , the IgE receptor was highly expressed in conducting airways but virtually absent in alveolar parenchyma. Conclusions: These findings demonstrate novel sitespecific subpopulations of lung MC TC and MC T at baseline conditions. This observation may have important implications in the future exploration of mast cells in a number of pulmonary diseases.