Novel site-specific mast cell subpopulations in the human lung

Background: Lung mast cells are stereotypically divided into connective tissue (MCTC) and mucosal (MCT) 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 characteristics of mast cell populations were investigated in multiple lung structures by immunohistochemistry and electron microscopy. Results: MCT and MCTC coexisted in all compartments, with MCT being the prevailing type in bronchi, bronchioles and the alveolar parenchyma and MCTC being more abundant in pulmonary vessels and the pleura. Each of the MCTC and MCT phenotypes could be further differentiated into site-specific populations. MCTC were significantly larger in pulmonary vessels than in small airway walls, while the reverse was observed for MCT. Within each MCTC and MCT population there were also distinct site-specific 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 MCT consistently expressed more histidine decarboxylase than alveolar MCT). Renin content was high in vascular MCTC but markedly lower in MCTC in other compartments. For both MCTC and MCT, the IgE receptor was highly expressed in conducting airways but virtually absent in alveolar parenchyma. Conclusions: These findings demonstrate novel site-specific subpopulations of lung MCTC and MCT at baseline conditions. This observation may have important implications in the future exploration of mast cells in a number of pulmonary diseases.