Inflammation of bronchial smooth muscle in allergic asthma

Abstract

Background: Recent observations in asthma suggest that bronchial smooth muscle is infiltrated by inflammatory cells including mast cells. Such an infiltration may contribute to airway remodelling that is partly due to an increase in smooth muscle mass. Whether muscle increase is the result of smooth muscle cell hypertrophy remains controversial and has not been studied by ultrastructural analysis. A morphometric analysis of airway smooth muscle (ASM) was undertaken in asthmatic patients using electron microscopy to examine the interactions between ASM cells and inflammatory cells. Methods: ASM specimens were obtained from 14 asthmatic subjects and nine non-asthmatic controls undergoing fibreoptic endoscopy. Inflammatory cell counts were assessed by immunohistochemistry, and ultrastructural parameters were measured using electron microscopy in a blinded fashion on smooth muscle cells and inflammatory cells. Results: ASM from asthmatic patients was infiltrated by an increased number of mast cells and lymphocytes. Smooth muscle cells and their basal lamina were thicker in asthmatic patients (9.5 (0.8) and 1.4 (0.2) mm) than in controls (6.7 (0.4) and 0.7 (0.1) mm). In asthmatics the extracellular matrix was frequently organised in large amounts between ASM cells. Myofibroblasts within smooth muscle bundles were only observed in asthmatics, some of them displaying a close contact with ASM cells. Conclusion: In asthma, airway myositis is characterised by a direct interaction between ASM cells and mast cells and lymphocytes. Smooth muscle remodelling was present, including cell hypertrophy and abnormal extracellular matrix deposition moulding ASM cells.

Mast Cell Fibroblastoid Differentiation Mediated by Airway Smooth Muscle in Asthma

“…This fibroblastoid transition was associated with an increase in gel contraction, which may be a consequence of cell size and function. This finding was consistent with earlier observations determined by electron microscopy whereby mast cells within the ASM bundle were found to be smaller with reduced granule content, as a consequence of piecemeal degranulation (17).…”

“…However, the CADM1-independent adhesion mechanism remains unexplained. Mast cells within the ASM bundle are in an activated state with increased IL-4 and IL-13 expression (15,16), are smaller than mast cells observed in the lamina propria, and undergo piecemeal degranulation as evidenced by electron microscopy (17). Whether these changes simply represent mast cell activation or a transition to an altered phenotype is unknown.…”

The mast cell and allergic diseases: role in pathogenesis and implications for therapy

“…Mechanisms involved are not completely understood and similar effects have not been reported on human lung mast cells, but presumably involve C3a activation and release of mast cell products that enhance ASM contraction [37]. In line with this observation, degranulated mast cells are found in the ASM of asthmatic patients and there may be a correlation between the number of degranulated mast cells and the severity of asthma as a greater number of degranulated mast cells are found in fatal cases of asthma [21,38].…”

“…In many instances, asthma has an allergic component characterized by allergic sensitivity to allergens and increased serum levels of antigenspecific IgE and total IgE. The role of the mast cell in asthma is of renewed interest due to reports that mast cell numbers are increased within the airway smooth muscle bundles of asthmatic patients [20][21][22][23][24][25]. This has led to a re-evaluation of the mast cell as a crucial effector cell in the pathogenesis of asthma, especially asthma with an allergic basis.…”

“…Mast cells numbers, but not T cells or eosinophils, are increased within the airway smooth muscle (ASM) of asthmatic patients [20,21,24,25]. The location of mast cells within the ASM is believed to facilitate hyper- [26,27].…”