August 23, 2004
The purpose of this workshop was to review the physiologic role of the brush microvillous absorptive cell type in normal airways and in respiratory diseases characterized by either excessive or insufficient amounts of airway fluid, (examples: cystic fibrosis, chronic bronchitis and exercise-associated asthma). With a better understanding of this pneumocyte's regulation of fluid and solutes across the respiratory mucosa and pleural surface, therapeutic strategies might be suggested that could optimize the amount and fluidity of surface secretions.
Many cells throughout the body have developed microvillous appendages for various tasks-sensing fluid flow through renal distal tubules, absorption, chemosensing or as a repair process of ciliated epithelial cells after injury (these differ from a brush or tuft cells). A brush cell has rootlet like projections as a tuft that form squat microvilli with filaments that stretch into the cells's cytoplasm; about 120-140 microvilli may be found on each cell, and the cell has a skewed or tilted position in tissue sections. They have been identified in the GI (about 0.3% cells) and respiratory tracts. Identification of brush cells has relied primarily on morphology with electron microscopy; they have a distinctive pear shape with a wide base, and a narrow microvillous apex. The function of brush cells is uncertain. The cells are rare. In rats, the highest density is in the vicinity of the broncholar alveolar junction (10%) and along the trachea/major bronchi (3%); they are present in the alveoli surface (1.5%). The airway and alveolar brush cells appear similar morphologically and are likely the same histological type, but their functions could be very different. In the kidney (proximal and distal tubules) there are no brush cells but lots of villous cells, a distinction that must be made in other organ tissues. Pleural mesothelial cells with brushy surface microvilli are likely different also. Pathologically, no disease state has been identified in which there has been an increase or apparent proliferation of brush cells.
- A rigorous, consensus definition of a "brush" cell is needed, discarding other descriptors such as a microvillous and caveolated. A "tuft" cell may be a preferable name.
- Morphology by transmission EM has been the standard for identifying brush cells, but searching for specific markers would be helpful. Staining with a variety of substances [cytokeratin, villin (an actin modulating protein), fimbrin] and viewing with light microscopy is suggested.
- With separation of a pure population of brush cells, microarray analysis would be important. Also, antigenic screening might be attempted by immunizing mice with a population of these cells and creating monoclonal antibody.
- Further identification of brush cells needs to be made in distal airway and alveolar tissue in normals and in diseased tissue, such as cystic fibrosis.
- Because of their high density in the area of the bronhchiolar alveolar junction, a location prominently involved with trapping inhaled particles or airway pollutants, brush cells might be involved in chemosensing or presenting antigens, thus involved in innate immunity. Possible progenitor cells could arise from Clara cells in the region. Experimental models should be developed to examine these interactions.
The meeting was held on August 23, 2004 in Bethesda, Maryland, USA
Chair: Lynne Reid, M.D., Harvard Medical School
- Veena Antony, M.D., University of Florida
- Richard Boucher, M.D., University of North Carolina at Chapel Hill
- James Crapo, M.D., National Jewish Medical and Research Center, Denver, Colorado
- Ling-Yi Chang, Ph.D., National Jewish Medical and Research Center, Denver, Colorado
- Michael Kashgarian, M.D., Yale School of Medicine
- E. R. McFadden, Jr., M.D., Case Western Reserve School of Medicine
- Barbara Meyrick, Ph.D., Vanderbilt University Medical Center
- Scott Randell, Ph.D., University of North Carolina at Chapel Hill
- Barry Stripp, Ph.D., University of Pittsburgh
- Jerrold Turner, M.D., Ph.D., University of Chicago
- Steve White, M.D., University of Chicago
- Herbert Reynolds, M.D., National Heart, Lung, and Blood Institute
- Stephen James, M.D., National Institute of Digestive and Kidney Diseases