Use of inhibitory (anti-catalytic) antibodies to study extracellular proteolysis

Hanning Birkedal-Hansen, Bente Birkedal-Hansen, Lester J. Windsor, Hong Yea Lin, Robert E. Taylor, William G.I. Moore

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The specific role of proteolytic enzymes in the degradation by live cells of fibrillar model matrices (fibrin, collagen) was studied using monoclonal and polyclonal inhibitory (anti-catalytic) antibodies. Dissolution of fibrin by plasminogen-supplemented human HT-1080 cells was blocked by (1) omission of plasminogen, (2) inhibitory anti-plasmin antibody, and (3) inhibitory anti-u-PA antibody but not by non-inhibitory control antibodies. Using a similar approach, it was shown that the dissolution of reconstituted type I collagen fibrils by trypsin-supplemented live human skin fibroblasts was blocked by inhibitory antibodies to fibroblast-type procollagenase but not by non-inhibitory control antibodies. These findings permit us to deduce that, at least in culture, the dissolution of fibrin by plasminogen-supplemented HT-1080 cells was mediated by plasminogen-assisted proteolysis which entailed the extracellular conversion of plasminogen to plasmin by cell-derived u-PA, and that the dissolution of collagen fibrils by trypsin-supplemented skin fibroblasts was mediated by a collagenase-dependent pathway.

Original languageEnglish (US)
Pages (from-to)211-224
Number of pages14
JournalImmunological Investigations
Issue number1-4
StatePublished - Jan 1 1989
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Birkedal-Hansen, H., Birkedal-Hansen, B., Windsor, L. J., Lin, H. Y., Taylor, R. E., & Moore, W. G. I. (1989). Use of inhibitory (anti-catalytic) antibodies to study extracellular proteolysis. Immunological Investigations, 18(1-4), 211-224.