Review
Elastin in asthma

https://doi.org/10.1016/j.pupt.2012.02.001Get rights and content

Abstract

Extracellular matrix is generally increased in asthma, causing thickening of the airways which may either increase or decrease airway responsiveness, depending on the mechanical requirements of the deposited matrix. However, in vitro studies have shown that the altered extracellular matrix produced by asthmatic airway smooth muscle cells is able to induce increased proliferation of non-asthmatic smooth muscle cells, which is a process believed to contribute to airway hyper-responsiveness in asthma. Elastin is an extracellular matrix protein that is altered in asthmatic airways, but there has been no systematic investigation of the functional effect of these changes. This review reveals divergent reports of the state of elastin in the airway wall in asthma. In some layers of the airway it has been described as increased, decreased and/or fragmented, or unchanged. There is also considerable evidence for an imbalance of matrix metalloproteinases, which degrade elastin, and their respective inhibitors the tissue inhibitors of metalloproteinases, which collectively help to explain observations of both increased elastin and elastin fragments. A loss of lung elastic recoil in asthma suggests a mechanical role for disordered elastin in the aetiology of the disease, but extensive studies of elastin in other tissues show that elastin fragments elicit cellular effects such as increased proliferation and inflammation. This review summarises the current understanding of the role of elastin in the asthmatic airway.

Section snippets

Changes to elastin in asthmatic airways

The series of case studies presented by Huber and Koessler in 1922 [34] which described the histology of 21 cases of asthma included several descriptions of elastin with findings ranging from increased, to unchanged, to decreased fibres. In more recent years there have been relatively few studies describing elastin in the airways of patients with asthma, and there is still no consensus in the literature about the alterations. Table 1 describes the recent body of data, showing the great

The role of elastin-degrading proteases in asthma

The role of proteases, particularly matrix metalloproteinases (MMPs), and their inhibitors is currently a key area of research focus in understanding asthma pathophysiology. Recent reviews have thoroughly explored the role of proteases in asthma and potential implications for treatment of MMPs (see [65], [66], [67], [68], [69], [70]) and neutrophil elastase (see [71], [72], [73]), so this paper will not attempt an exhaustive review. However, some key findings relating to elastin degradation are

Biological effects of elastin fragments and new elastin

Elastin fragments are matrikines, which are fragments of ECM with biological activity that are produced upon degradation. The biological effects of degraded elastin on cells support an overall inflammatory and remodelling profile [31], [32], [95], [96]. Some of the effects of elastin are summarised in Table 2. Elastin fragments are identified as chemotactic for monocytes [97], [98] and alveolar macrophages [98] and promote migration of granulocytes [99], suggesting that damage to elastin

Conclusion

Elastin is a structural ECM protein which is expressed in the lung and may play a crucial part in regulating the cellular behaviour in this organ either as a whole protein or fragments thereof. Studies that report on the status of elastin in asthmatic airways, either examining biopsies or tissue obtained from autopsies, reveal changes to elastin ranging between decreased and fragmented fibres [3], [38], [40], [46], [57], increased elastic fibre or bundle content [40], [43], [47], [53], and

Acknowledgements

JKB is supported by a National Health and Medical Research Council, Australia R. Douglas Wright Fellowship #402835. ASW acknowledges support from the Australian Research Council and the National Health & Medical Research Council Australia.

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