Features
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Measures endogenous active MMP-8 ( naturally occurring ) or total active MMP-8 ( following activation with APMA ).
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Samples: cell culture conditioned medium, serum, plasma, urine, saliva and tissue homogenates.
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Quantitative.
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Range: 10 – 24000 pg/ml.
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Sensitivity: 100 pg/ml for 2 h incubation with detection reagent; 24 pg/ml for 6 h incubation with detection reagent; 4 pg/ml for 24 h incubation with detection reagent.
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Ease-of-use: Equivalent to ELISA.
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Marker for neutrophils (PMN)
Research topic
Atherosclerosis, Cardiovascular disease, Extracellular matrix, Immune Response, Infection and Inflammation, Oncology, Pulmonary diseases
Summary
Matrix metalloproteinase-8 (MMP-8; called also neutrophil collagenase or collagenase 2) is
a member of matrix metalloproteinase family of zinc- and calcium-dependent endo-peptidases
responsible for degradation of extracellular matrix. Matrix metalloproteinases (MMPs) possess
catalytic properties responsible for tissue remodeling and degradation of structural components
of the extracellular matrix (ECM) including collagens, elastins, gelatin, matrix glycoprotein,
and proteoglycans.
MMP-8 was first described (as neutrophil collagenase) in 1990 when it was cloned
from neutrophils obtained from a patient with granulocytic leukemia. Later observations
found MMP-8 mRNA expression in chondrocytes as well as in human rheumatoid synovial
fibroblasts, activated macrophages, smooth muscle cells and endothelial cells.
The human MMP-8 gene is located on chromosome 11q22.3, residing in a gene cluster that
contains several MMP genes. Its expression is inducible and upregulated by various
inflammatory cytokines, such as interleukin-1β, tumour necrosis factor-α, and CD40 ligand.
The MMP-8 protein consists of a signal peptide, a propeptide, a catalytic domain, a hinge
region, and a hemopexin-like C-terminal domain. The mature MMP-8 enzyme is 64 kDa
in size, with glycosylation increasing the size to 75 kDa. Autoproteolytic degradation has been
described, yielding a 40-kDa fragment, which retains catalytic activity but does not cleave
fibrillar collagen. MMP-8 can be proteolytically activated also by stromelysin-1 (MMP-3),
stromelysin-2 (MMP-10) and by matrilysin-1 (MMP-7).
PMN-derived MMP-8 is expressed during the myelocyte stage of development
of polymorphonuclear (PMN) precursors in the bone marrow, and it is stored as a latent
enzyme (pro-MMP-8) within the specific granules of polymorphonuclear cells. Pro-MMP-8 is
rapidly released from activated PMN undergoing degranulation, and is then activated via the
cysteine switch mechanism to yield the active form of the enzyme to ensure rapid availability
at inflammatory sites. The endogenous MMP inhibitors, TIMPs, can inhibit MMP-8.
Therefore, the activity of MMP-8 in a tissue at a given time would be dependent on the relative
amounts of its transcriptional stimuli, zymogen activators and enzymatic inhibitors that are
present in that tissue at the time.
The best-known substrates of MMP-8 are interstitial collagens (types I-III), the major
structural components of the extracellular matrix, among which MMP-8 has higher proteolytic
activity on types I and III than type II. In addition, MMP-8 can also cleave nonmatrix
proteins such as serpins, bradykinin, angiotensin I, fibrinogen and many other.
As a result of its known catalytic activities, MMP-8 is believed to be involved in wound healing
and tissue remodeling during inflammation. In addition, MMP-8 has been implicated in the
pathogenesis of several chronic inflammatory diseases characterized by excessive influx
and activation of polymorphonuclear cell (PMN), including cystic fibrosis, rheumatoid arthritis,
chronic skin wounds and periodontal disease.
The number of publications investigating the role of MMPs in periodontal disease has
been still growing. The imbalance between MMPs and tissue inhibitors of matrix
metalloproteinases (TIMPs) is considered to trigger the degradation of extracellular matrix,
basement membrane, and alveolar bone, and thus to initiate periodontal disease. MMP-8
was found to be the most prevalent MMP in diseased periodontal tissue, oral fluid, gingival
crevicular fluid (GCF) and saliva. Moreover, MMP-8 activity correlates with disease severity
. Reduction of MMP activity was shown to reduce periodontitis progression. MMP-8 is
apparently a major mediator of this aggressive tissue destruction, although one report indicates
a protective role for MMP-8 during periodontal infection.
