Fibroblasts and asthma

The symptoms of bronchial asthma relate to airways obstruction which may be either episodic or chronic. Pharmacological [1,2] and. more recently, pathological studies [3,4] have demonstrated the inadequacy of the simple model of IgE-mediated mast cell degranulation as an explanation of the complexities of bronchial asthma. In particular, immunopathological studies have demonstrated that the airway inflammation previotisly associated with fatal asthma occurs during life in mild asthma. Pathological studies of bronchial biopsy specimens have confirmed the apparent thickening ofthe bronchial epithelial basement membrane [5,6] which was previously reported in autopsy studies of fatal acute severe asthma [7,8]. It is now evident that this phenomenon occurs in mild atopic asthma even with a relatively short clinical history. This characteristic appearance had been ascribed previously to chronic epithelial cell damage, leading to the synthesis of new basement membrane components, akin to the microvaseular damage in diabetes mellitus [9]. This view had persisted, despite ultrastructural studies which had shown that the true epithelial basement membrane was normal and that the apparent thickening was due to the deposition of fibrillar collagen species leading to an increase in the depth and density of the lamina reticularis [6.10], which lies beneath the basement membrane proper (Fig. 1). Further sludies in larger numbers of patients have confirmed that this abnormal layer in asthma is composed of interstitial collagens [4,11]. A detailed immunohistochemical study has shown that collagens III and V and, to a lesser extent collagen I, contribute to this thickening and that the epithelial basement membrane components, collagen IV and Iaminin. are absent [II]. These findings indicate that this layer is composed of the structural collagens of mesenchymal connective tissue. The presence of these interstitial components has led to a search for a mesenchymal celi that might secrete collagens beneath the epithelial basement membrane in asthma. An analogy