|
|
|
Instructions,
| The Relationship of The Attenuated Fibroblast Sheath of the Respiratory Tract to Inhalation Toxicology) (bELOW IS A THUMBNAIL OF THE FIGURE - CLICK TO ENLARGE) The broad field of inhalation toxicology includes the study of the biological response of the lungs to inhaled materials. The relationship between the morphology of the lung and particle deposition is summarized in the last newsletter. A newly identified morphological component of the lung, the attenuated fibroblast sheath or AFS is described in this note. Although the study of the AFS is still in its infancy, it appears that responses of local cell populations to inhaled materials may be regulated by the AFS. In addition, due to its potential to function as a single unit, the AFS may coordinate the response of cells immediately affected by inhaled materials deposited throughout the entire airway tree. The study of organ structure and its relationship to cellular function in the lung is less advanced than in other organs. The primary reason for this is the heterogeneity of cell types and their varying distribution by airway level throughout the lung. In addition, cell proliferation patterns and the identification of stem cells is difficult due to the slow turnover of lung cells in general. These areas often require careful electron microscopic studies. With these factors in mind, the interstitium, or area between the epithelial basement membrane and the endothelium of the blood vessels has been even less studied than the epithelium until relatively recently. It is known, however, that interactions between all components of the lung including epithelial, neural, mesenchymal (including fibroblasts) and extracellular matrix are necessary for lung functions such as growth, cell differentiation, repair from injury, as well as disease development. Subpopulations of fibroblasts have been identified that play a role in asthma and its related fibrosis. Fibroblasts have also been shown to synthesize cytokines and chemotactic agents and this synthesis has been shown to vary in relation to proximity to the airway wall. The presence of the attenuated fibroblast sheath (AFS) around the basement membrane of the trachea in all species studied, including humans, was reported in 1993. Figure 1 above is a diagram of the AFS as it was mapped in the tracheal region. These attenuated fibroblasts are large flat mesenchymal cells that intermesh closely and contact the basement membrane in numerous places. In the most recent study of these cells, a 3 dimensional model was constructed of attenuated fibroblasts around the airways, extending from the trachea down to the terminal bronchioles and continuing into the alveolar walls. This long mesenchymal sheath surrounds at least 70% of the airways and is defined now as a unique anatomic unit. The AFS consists of large flat stellate shaped fibroblasts and myofibroblasts adjacent to the basement membrane. Other fibroblasts are still present in the interstitium; however these are spindle shaped. The basement membrane separates the AFS from the epithelium. This spatial relationship between the epithelium and AFS is always maintained suggesting that these cells are anchored in place and yet communicate between each other. In part because of this constant spatial relationship, the AFS is thought to interact with many components of the lung including epithelial, inflammatory cells and neural tissues. Because of all these potential interactions, which could be involved in growth, differentiation, repair and regulation of the cellular response to injury, the AFS in conjunction with the epithelium is now been termed the epithelial-mesenchymal-trophic unit (EMTU). The EMTU is postulated to allow local exchange of information between different anatomic components of the lung as well as allowing cells to respond to both internal and external stimuli. Possible means of cell-to-cell communication include soluble mediators, adhesion plaques between matrix and cell, and gap junctions. Currently information is lacking on EMTU functions in vivo. However it is likely the AFS is involved in the airway remodeling of the entire EMTU that occurs in asthmatic humans. In vitro studies of AFS cells indicate that they synthesize and secrete granulocyte-macrophage colony stimulating factor, interleukin 8, and stem-cell factor in response to tumor necrosis factor. Human bronchial epithelial cells that are plated on a collagen gel of AFS form a coculture that resembles the EMTU in vivo. Injury to these epithelial cells results in release of growth factors controlling myofibroblast proliferation. The AFS is similar to structures in other organs including kidneys, liver, endometrium, synovium, and breast where they are in a class of subepithelial cells called juxtaparenchymal cells. The identification and initiation of studies of both the AFS and EMTU of the lung is an advance in understanding pulmonary responses to toxic and pharmacologic agents regardless of route of administration. The presence of the EMTU suggests that morphological studies of the lung should include more than epithelium or endothelium. Tissue culture models of the lung might also be more accurate if designed, not only with the epithelial cells, but also if the adjacent EMTU or equivalent matrix in the system were included as well. References: The Attenuated Fibroblast Sheath of the Respiratory Tract Epithelial-Mesenchymal Trophic Unit. 1999. Michael J. Evans, Laura S. Van Winkle, Michelle V. Fanucchi, Charles G. Plopper. Am J Respir Cell Mol Biol. 21: 665-657 (Dec, 1999). www.atsjournals.org Zhang, S., H. Smarti, S.T. Holgate, and W.R. Roche. 1999. Growth factors secreted by bronchial epithelial cells control myofibroblast proliferation: an in vitro co-culture model of airway remodeling in asthma. Lab. Invest. 79:395-405. By: Susan G. Shami, Sc.D. Illustration: Susan G. Shami. Sc.D.
|
