Research Article
Metalloproteinases and Their Tissue Inhibitors in Comparison
between Different Chronic Pneumopathies in the Horse
Ann Kristin Barton,
1
Tarek Shety,
1
Angelika Bondzio,
2
Ralf Einspanier,
2
and Heidrun Gehlen
1
1
Equine Clinic, Veterinary Faculty, Freie Universitaet Berlin, Oertzenweg 19b, 14163 Berlin, Germany
2
Institute of Veterinary Biochemistry, Veterinary Faculty, Freie Universitaet Berlin, Oertzenweg 19b, 14163 Berlin, Germany
Correspondence should be addressed to Ann Kristin Barton; ann-kristin.barton@fu-berlin.de
Received 30 July 2015; Revised 13 November 2015; Accepted 17 November 2015
Academic Editor: Kang-Yun Lee
Copyright © 2015 Ann Kristin Barton et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
In chronic respiratory disease, matrix metalloproteinases (MMPs) contribute to pathological tissue destruction when expressed in
excess, while tissue inhibitors of metalloproteinases (TIMPs) counteract MMPs with overexpression leading to fbrosis formation.
Tey may be out of balance in equine pneumopathies and serve as biomarkers of pulmonary infammation. We hypothesized
that MMPs and TIMPs correlate to clinical fndings and bronchoalveolar lavage fuid cytology in diferent equine chronic
pneumopathies. Using a scoring system, 61 horses were classifed controls as free of respiratory disease ( = 15), recurrent airway
obstruction (RAO, = 17), infammatory airway disease (IAD, = 18), or chronic interstitial pneumopathy (CIP, = 11).
Zymography and equine MMP and TIMP assays were used to detect MMP-2, MMP-8, MMP-9 as well as TIMP-1, and TIMP-2
in BALF supernatant. MMP-2, TIMP-1, and TIMP-2 concentrations were signifcantly increased in RAO and IAD compared to
controls. MMP-9 concentration and MMP-8 activity evaluated by fuorimetry were signifcantly increased in RAO, IAD, and CIP.
Tese results were confrmed by zymography for MMP-2 and MMP-9 activity in 52 horses. In conclusion, MMPs and TIMPs
correlate well with clinical and cytologic fndings. Tese fndings support the usefulness of MMPs, TIMPs, and their ratios to
evaluate the severity of respiratory disease and may help to identify subclinical cases.
1. Introduction
Te extracellular matrix (ECM) represents the scafold that
supports the alveolar wall and has a major impact on
lung architecture, homeostasis, and function. Te pulmonary
ECM underlays a continuous turnover; a dynamic equilib-
rium between synthesis and degradation of the ECM is main-
tained for physiological balance. Tis balance is controlled
by synthesis and deposition of ECM components, proteolytic
degradation of ECM by matrix metalloproteinases (MMPs),
and inhibition of MMP activity by specifc tissue inhibitors of
matrix metalloproteinases (TIMPs) [1–3]. In health, MMPs
degrade the ECM to allow normal tissue repair, but in
chronic infammation they contribute to pathological tissue
destruction when expressed in excess [4]. Tus, it has been
suggested that MMPs can either protect against or contribute
to pathology in infammatory processes by exacerbation of
aberrant lung remodeling [5–7]. ECM degradation results in
destruction of interstitial collagen and release of degraded
collagen fragments, which results in neutrophil infux with
the production of chemoattractants [8]. In chronic res-
piratory disease, remodeling results in decreasing airway
lumen, increased smooth muscle mass, peribronchial fbrosis,
epithelial cell hyperplasia, and impaired airway function [9–
11]. Regulation of remodeling may be a key for developing
new therapeutics and disease management [2].
Matrix metalloproteinases (MMPs) were frst described
over 50 years ago by Gross and Lapiere [12]. Collagenolytic
MMP-8 was increased in tracheal epithelium lining fuid
(TELF) of RAO afected horses [13]. Immunoreactivity of
collagenases MMP-8 and MMP-13 was signifcantly increased
in TELF of horses with RAO, compared to healthy horses, and
was positively correlated with the amount of degradation of
type-I collagen [14].
Hindawi Publishing Corporation
Mediators of Inflammation
Volume 2015, Article ID 569512, 9 pages
http://dx.doi.org/10.1155/2015/569512