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

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

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)223-231
Number of pages9
JournalConnective Tissue Research
Volume50
Issue number4
DOIs
StatePublished - Sep 3 2009

Keywords

  • Complex Formation
  • ELISAs
  • MMP
  • MMP:TIMP Complexes
  • Plasma
  • TIMP

ASJC Scopus subject areas

  • Rheumatology
  • Biochemistry
  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

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