Eosinophils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation.

Ohno, Isao; Ohtani, Haruo; Nitta, Yuko; Suzuki, Jun; Hoshi, Hideo; Honma, Masaaki; Isoyama, Shigemi; Tanno, Yasuo; Tamura, Gen; Yamauchi, Kohei; Nagura, Hirosi; Shirato, Kunio

doi:10.1165/ajrcmb.16.3.9070604

Cited by 209 publications

(158 citation statements)

References 22 publications

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“…They are secreted together by bronchial epithelial cells, bind in a 1:1 ratio, and can be modulated by inflammatory mediators and cytokines (16)(17)(18)(39)(40)(41). A high MMP-9͞TIMP-1 ratio in bronchoalveolar lavage fluid indicates collagen degradation, inflammation, and poor prognosis, whereas higher TIMP-1 correlates with tissue repair and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Mechanical stress is communicated between different cell types to elicit matrix remodeling

Swartz

Tschumperlin

Kamm

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

241

158

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Tissue remodeling often reflects alterations in local mechanical conditions and manifests as an integrated response among the different cell types that share, and thus cooperatively manage, an extracellular matrix. Here we examine how two different cell types, one that undergoes the stress and the other that primarily remodels the matrix, might communicate a mechanical stress by using airway cells as a representative in vitro system. Normal stress is imposed on bronchial epithelial cells in the presence of unstimulated lung fibroblasts. We show that (i) mechanical stress can be communicated from stressed to unstressed cells to elicit a remodeling response, and (ii) the integrated response of two cell types to mechanical stress mimics key features of airway remodeling seen in asthma: namely, an increase in production of fibronectin, collagen types III and V, and matrix metalloproteinase type 9 (MMP-9) (relative to tissue inhibitor of metalloproteinase-1, TIMP-1). These observations provide a paradigm to use in understanding the management of mechanical forces on the tissue level.airway wall remodeling ͉ airway epithelium ͉ asthma ͉ lung fibroblasts I n the past two decades, it has been well established that many cells are sensitive to mechanical forces and can change their phenotype and surrounding extracellular matrix (ECM) in response to changes in their mechanical environment. However, it has not been established how mechanical forces are managed on a tissue level, in which different cell types share a common ECM and may alter their mechanical environment by inducing other cells to remodel the ECM.The airway wall is an example of a mechanically active tissue (e.g., bronchoconstriction) composed of multiple cell types that share a common extracellular matrix. It is known that patients with poorly controlled asthma develop structural changes in the airway wall: the subepithelial layers significantly thicken (1-4) and there is deposition of collagen types III and V, among other fibrous proteins, beneath the basement membrane (4, 5). The major consequences of airway remodeling are altered tissue mechanics and airway hyperresponsiveness (6).The remodeling process in asthma has been attributed to the effects of the inflammatory response that characterizes the disease, but this sequence of events has only been inferentially established. We propose an alternative hypothesis for airway wall remodeling in asthma, namely that the mechanical stress associated with bronchoconstriction that is imposed on bronchial epithelial cells could, itself, stimulate and amplify airway wall remodeling in the absence of inflammatory agents. Specifically, we hypothesize that, when airway epithelial cells are subjected to mechanical stress, they act in concert with subepithelial fibroblasts to modulate the fibrous structure of the airway in response to this mechanical stress.This hypothesis, if true, would provide two key insights. First, it would challenge the idea that airway wall remodeling in asthma is solely the consequence of inflam...

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Section: Discussionmentioning

confidence: 99%

Mechanical stress is communicated between different cell types to elicit matrix remodeling

Swartz

Tschumperlin

Kamm

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

241

158

View full text Add to dashboard Cite

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“…MMP-9 can be produced by neutrophils, monocytes, macrophages and epithelial cells, and is a marker of lung injury. In addition, there is evidence for eosinophil degranulation in bronchiectasis [22] and eosinophil granules also contain collagenases [23], including MMP-9, which is capable of degrading type IV collagen [24]. Furthermore, release of eosinophil major basic protein (MBP) can induce neutrophil degranulation and IL-8 production [25].…”

Section: Discussionmentioning

confidence: 99%

Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis

Gibson¹,

Wark²,

Simpson³

et al. 2003

Eur Respir J

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Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus, causing severe asthma that may progress to bronchiectasis. Sputum neutrophilia can occur in association with sputum eosinophilia and correlates with the degree of bronchiectasis. The mechanisms of sputum neutrophilia in ABPA are not known. The aim of this study was to investigate the role of the chemokine interleukin (IL)-8 in sputum neutrophilia in ABPA.Induced sputum was obtained from subjects with ABPA (n=29), and compared to nonsensitised asthma (n=9) and healthy controls (n=21). Semiquantitative polymerase chain reaction was used to assess IL-8 gene expression in induced sputum and IL-8 protein was measured by enzyme-linked immunosorbent assay.Sputum IL-8 protein was significantly higher in ABPA compared to asthma and controls. IL-8 messenger ribonucleic acid/glyceraldehyde-3-phosphate dehydrogenase ratio was elevated in ABPA compared to asthma and controls. Sputum IL-8 correlated with sputum neutrophils, matrix metalloproteinase-9 levels and forced expiratory volume in one second.Interleukin-8 gene expression and protein release were increased in allergic bronchopulmonary aspergillosis and correlated with airway neutrophilia and airway obstruction. The interleukin-8-mediated neutrophil influx in allergic bronchopulmonary aspergillosis may induce lung damage via release of matrix metalloproteinase-9, potentially leading to bronchiectasis. Eur Respir J 2003; 21: 582-588.

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“…The increased MMP-9 activity observed in the airways of asthmatic patients seems related to an increased number of granulocytes and more precisely neutrophils in the airways rather than to an enhancement of MMP-9 secretion by those cells (Cataldo et al, 2001;Prause et al, 2004). Other authors have suggested that eosinophils, key cells in asthma-related airway inflammation, could also be a major source for MMP-9 in this disease (Ohno et al, 1997). A significant correlation was indeed found in immunohistochemistry and in situ hybridisation between MMP-9 expression and eosinophil counts in bronchial mucosa.…”

Section: Implication Of Mmps In the Pathogenesis Of Asthmamentioning

confidence: 92%

“…A significant correlation was indeed found in immunohistochemistry and in situ hybridisation between MMP-9 expression and eosinophil counts in bronchial mucosa. MMP-9 is also expressed by bronchial epithelium and may be an important factor promoting eosinophilic infiltration into the airways from patients suffering from asthma (Han et al, 2003;Ohno et al, 1997). Although the interest of investigating a balance between MMP-9 and TIMP-1 would probably be restricted to the pericellular area, some authors have reported an imbalance observed between MMP-9 and TIMP-1 measured in bronchial secretions or bronchoalveolar lavage, with a significant increase of TIMP-1 production when compared to that of MMP-9, thought to favouring extracellular matrix deposition (Mautino et al, 1999;Vignola et al, 1998b).…”

mentioning

confidence: 99%

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

Guéders

Foidart

Noël

et al. 2006

European Journal of Pharmacology

278

224

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In healthy lung, Matrix Metalloproteinases (MMPs) and their physiological inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs), are produced in the respiratory tract by a panel of different structural cells. These activities are mandatory for many physiological processes including development, wound healing and cell trafficking. Deregulation of proteolytic-antiproteolytic network and inappropriate secretion of various MMPs by stimulated structural or inflammatory cells is thought to take part to pathophysiology of numerous lung diseases including asthma, chronic obstructive pulmonary disease (COPD), lung fibrosis and lung cancer. Cytokines and growth factors are involved in these inflammatory processes and some of those mediators interact directly with MMPs and TIMPs leading either to a regulation of their expression or changes in their biological activities by proteolytic cleavage. In turn, cytokines and growth factors modulate secretion of MMPs establishing a complex network of reciprocal interactions. Every MMP seem to play a rather specific role and some variations of their expression are observed in different lung diseases. The precise role of these enzymes and their inhibitors is now studied in depth as they could represent relevant therapeutic targets for many diseases. Indeed, MMP inhibition can lead either to a decrease of the intensity of a pathological process or, in the contrary for some of them, to an increase of disease severity. In this review, we focus on the role played by MMPs and TIMPs in asthma and we provide an overview of their potential roles in COPD, lung fibrosis and lung cancer, with a special emphasis on loops including MMPs and cytokines and growth factors relevant in these diseases.Keywords: Matrix metalloproteinase; Tissue inhibitor of MMP; Asthma; Cytokine; Growth factors Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)Matrix metalloproteinases (MMPs), or matrixins, belong to the metzincin superfamily of metalloproteinases, also including astacins, ADAMs (a protein with a disintegrin and metallopro-tease domain) and ADAM-TS proteases (ADAM with a thrombospondin-like motif) (Sternlicht and Werb, 2001;Folgueras et al., 2004;Handsley and Edwards, 2005;Noel et al., 2004). MMPs are proteolytic enzymes believed to be implicated in many physiological and pathological processes including embryonic development, morphogenesis, reproductive processes, bone remodeling, wound healing, cancer, arthritis, atherosclerosis, MMPs are zinc and calciumdependent enzymes being able to degrade virtually all extracellular matrix components. This can modulate cell behaviour by creating influential cellular environment (Shapiro, 1998). The extracellular matrix is a complex network of molecules including collagens, fibronectin, laminin, entactin/ nidogen and heparan sulfate proteoglycans (Mott and Werb, 2004). The extracellular matrix is a mechanical support for cells but also acts as a reservoir for cytokines and growth factors (vascular endothelial ...

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Eosinophils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation.

Cited by 209 publications

References 22 publications

Mechanical stress is communicated between different cell types to elicit matrix remodeling

Mechanical stress is communicated between different cell types to elicit matrix remodeling

Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

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