American Review of Respiratory Disease

Over the past decade, it has become increasingly recognized that airways inflammation is one of the major components of asthma. Until recently, measurements of bronchial responsiveness and mediators of allergic reactions were the only methods of studying pathogenetic mechanisms in asthma. With improved diagnostic procedures such as fiberoptic bronchoscopy, it has become possible to investigate these mechanisms and the resulting inflammatory changes in situ. BAL has highlighted the presence of mast cells and eosinophils and has given proof of their mediator participation in airways inflammation and hyperresponsiveness. Endobronchial biopsies have so far yielded results that are similar to those obtained from postmortem studies, although it appears that there are varying degrees of inflammation in living asthmatics. Even in mild disease, the histopathologic features of bronchial asthma are consistent with chronic inflammation. Indirect evidence obtained from allergen challenge leading to increased bronchial hyperresponsiveness during LAR, and direct evidence of inflammatory cells and their mediators in the airway mucosa and lumen after allergen challenge argue for an active role of cells in bringing about inflammatory changes. At present, however, it is not possible to relate precisely the findings obtained by bronchoscopy to the clinical presentation and progression of asthma. Cell activation with production of potent mediators of inflammation may be more relevant to inflammation than the simple presence of these cells in the airways.

Almost all the inflammatory cells present in the bronchial wall and lumen have been implicated in the pathogenesis of mucosal inflammation in asthma, but with our current state of knowledge, none can be singled out as the most important contributor. The mast cell was the first to be investigated in depth, and despite the accumulation of large amounts of data concerning its ultrastructure and function, it remains uncertain to what extent this cell is involved in inflammatory responses. Thus, while its main role appears to be that of initiator of allergen-induced responses, the eosinophil has attracted more attention as a proinflammatory cell rather than as an antiinflammatory cell with a capacity to be selectively recruited from the circulation in response to IgE-dependent signals. The eosinophil secretes potent mediators that cause damage to the bronchial epithelium and lead to bronchoconstriction.

The role of other cells is at present not as well defined. In humans, evidence of the role of the neutrophil is less firm than that for the eosinophil, but animal studies suggest that, at least in some species, the neutrophil plays a significant part in allergic airways inflammation. Macrophages, which possess low-affinity receptors for IgE like eosinophils, also have a place in asthma pathogenesis, but whether their proinflammatory role or ability to regulate immunologic responses in the airways is more important remains to be elucidated. There is also need for further studies into the role of platelets that possess IgE receptors and by virtue of their mediators could participate in inflammatory responses. Finally, cell-cell cooperation is necessary to orchestrate the events that result from allergen exposure and that lead to bronchial inflammation. In this respect, all the above mentioned cells have a place in what appears to be a complex intercellular network of signals, with lymphocytes possibly playing the most important role as immunoregulators.


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