Abstract

Background: 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 characteristics 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 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 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 site-specific 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.