MMP-8 ELISA Kit, Human

BACKGROUND Matrix metalloproteinase-8 (MMP-8, collagenase-2, EC 3.4.24.34, also called neutrophil collagenase,) along with MMP-1 and MMP-13 are the major members of the interstitial collagenase subgroup of the MMP family of zinc-dependent, neutral proteinases. Interstitial collagens (types I-III) are major structural components of the extracellular matrix (ECM).¹ They are composed of three polypeptide chains arranged in a rigid triple helix conformation, rendering them resistant to degradation by proteinases other than the interstitial collagenases. Interstitial collagenases mediate the initial and rate-limiting step in interstitial collagen degradation by cleaving the three collagen polypeptide chains at a single locus three-fourths of the distance of the collagen molecule from its N-terminal end. The three-fourth and one-fourth fragments generated denature spontaneously, and the denatured collagen fragments (gelatins) are susceptible to further cleavage by gelatinases (MMP-2 and MMP-9) and to a lesser extent by other MMPs (including MMP-8) and serine proteinases. Although MMP-8 cleaves all three interstitial collagens, it differs from MMP-1 in that it cleaves type I collagen at a higher rate than type III collagen. MMP-8 also degrades type II collagen, the predominant collagen of cartilage, at a higher rate than MMP-1. MMP-8 can also cleave nonmatrix proteins such as serpins, bradykinin, angiotensin I, and substance P. Polymorphonuclear cells (PMNs) are the main source of MMP-8 in humans. However, MMP-8 is also expressed at lower levels by chondrocytes, rheumatoid synovial fibroblasts, activated macrophages, smooth muscle cells, and endothelial cells. PMN-derived MMP-8 differs from interstitial collagenases expressed by other cells in that it is not synthesized de novo by mature PMN. Rather, MMP-8 is expressed during the myelocyte stage of development of PMN precursors in the bone marrow, and it is stored as a latent enzyme (pro-MMP-8, Mr 85 kDa) within the specific granules of PMN. 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 (Mr _65 kDa). Activation can be achieved in vitro by organomercurials, serine proteinases. Moreover, MMP-8 is expressed on the cell surface of activated PMN, and this form of the proteinase can contribute to potent, TIMP-resistant pericellular collagenase and serpinase activity.²

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, periodontal disease, and chronic skin wounds. In addition, MMP-8 is also produced by endothelial cells and is present within atherosclerotic lesions. It palys prominent role in inflammatory and vascular diseases. In addition, it was demonstrated that MMP-8 has an unexpected role in vivo in protecting male mice from the development of skin tumors in a chemical carcinogenesis model.³

 

REFERENCES  

1. Chakraborti, S. et al: Mol Cell Biochem. 253:269-85, 2003
2. Owen, C.A. et al: J. Immunol. 172:7791–803, 2004
3. Balbín, M. et al: Nat. Genet.35:252-7, 2003 
 

 

ELISA Kits are based on standard sandwich enzyme-linked immunosorbent assay technology. Freshly prepared standards, samples, and solutions are recommended for best results.