EOSINOPHILS AS A SOURCE OF MATRIX METALLOPROTEINASE-9 IN ASTHMATIC AIRWAY INFLAMMATION

Bronchial asthma is characterized by eosinophil infiltration and tissu e remodeling. Matrix metalloproteinases (MMPs) are thought to play cri tical roles by degradating interstitial matrices in a wide range of lu ng diseases associated with reorganization of the airway architecture. To investigate whether MMPs are involved in the pathologic processes of bronchial asthma, we examined MMP expression in asthmatic subjects. In situ hybridization revealed abundant expression of MMP-9 (gelatina se B) mRNA in biopsy specimens from asthmatic subjects (n = 5), with a n average positive cell distribution of 117.8 +/- 41.1 (mean +/- SEM)/ mm(2). In contrast, sparse expression of the mRNA (10.8 +/- 4.8/mm(2)) was observed in specimens from normal subjects (n = 4). The vast majo rity of cells expressing the mRNA were eosinophils in asthmatic tissue s (92.2 +/- 1.2%). MMP-9 protein, which was confined to the submucosal cells in the normal subjects, was not abundantly expressed in inflamm atory cells, but there was positive reactivity for MMP-9 protein in th e extracellular matrix. Immunoelectron microscopic analysis showed spa rse immunolocalization of MMP-9 in the perinuclear spaces of eosinophi ls, but not in the granules. These findings suggest the overexpression of MMP-9 by eosinophils in bronchial tissues of asthmatic individuals , and the participation of MMPs in the pathologic changes in asthmatic airways.