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Zucker, S. et al.

Stanley Zucker, Cathleen E. Schmidt, Antoine Dufour, Robert C. Kaplan, Hyun I. Park, Weiping Jiang,

ProMMP-2: TIMP-1 complexes identified in plasma of healthy individuals.

Activation of MMPs in tissues is an important component of tissue injury. Based on earlier reports that (latent) proMMP-2 is incapable of forming a complex with TIMP-1, we reasoned that the identification of MMP-2:TIMP-1 complexes in blood might serve as a surrogate marker ("smoking gun") of MMP-2 activation in tissues. Using specific antibodies, we developed a sensitive and specific assay to detect MMP-2:TIMP-1 complexes. We were perplexed to find that approximate 40% of plasma specimens from healthy individuals had detectable levels of the MMP-2:TIMP-1 complexes. Employing recombinant TIMP-1 bound Sepharose beads and Western blots, we demonstrated binding between recombinant proMMP-2 and TIMP-1 proteins. Recombinant MMP-2 lacking the catalytic domain also bound to TIMP-1 coated beads. These data are consistent with TIMP-1 binding to the hemopexin or hinge domain of proMMP-2. The explanation for the presence of plasma proMMP-2:TIMP-1 complexes in selected healthy individuals remains to be determined. In contrast to our immunoassay and bead-binding experiments, proMMP-2 failed to bind to immobilized TIMP-1 employing surface plasmon resonance technology. Additional studies are needed to clarify these contrasting results.[1]

References

ProMMP-2: TIMP-1 complexes identified in plasma of healthy individuals. Zucker, S., Schmidt, C.E., Dufour, A., Kaplan, R.C., Park, H.I., Jiang, W. Connect. Tissue Res. (2009) [Pubmed]

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