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Published online before print May 22, 2003

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© 2003 by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0203086

Received for publication February 28, 2003.
Revised March 7, 2003.
Accepted for publication March 17, 2003.

Article

Proteinase-3 directly activates MMP-2 and degrades gelatin and Matrigel; differential inhibition by (-)epigallocatechin-3-gallate

Elga Pezzato ^*, Massimo Donà ^*, Luigi Sartor ^*, Isabella Dell'Aica ^*, Roberto Benelli , Adriana Albini , and Spiridione Garbisa ^*@

*Department of Experimental Biomedical Sciences, Medical School, Padova, Italy; and Molecular Biology Laboratory, National Institute for Research on Cancer, IST, Genova, Italy

^@ To whom correspondence should be addressed. E-mail: garbisa{at}unipd.it.

	Abstract

Proteinase-3 (PR-3), a serine-proteinase mainly expressed by neutrophils (PMNs), can degrade a variety of extracellular matrix proteins and may contribute to a number of inflammation-triggered diseases. Here, we show that in addition to Matrigel^TM components, PR-3 is also able to degrade denatured collagen and directly activate secreted but not membrane-bound pro-MMP-2, a matrix metallo-proteinase instrumental to cellular invasion. In contrast, following addition of purified PR-3 or PMNs to HT1080 tumor cells, dose-dependent inhibition of in vitro Matrigel^TM invasion is registered. (-)Epigallocatechin-3-gallate (EGCG), the main flavanol in green tea and known to inhibit inflammation and tumor invasion, exerts dose-dependent inhibition of degradation of gelatin (IC₅₀<20 µM) and casein, which is directly triggered by PR-3. The presence of EGCG does not modify the colocalization of MMP-2 and exogenous PR-3 at the cell surface and does not restrain secreted pro-MMP-2 and pro-MMP-9 activation or degradation of a specific, synthetic peptide by PR-3. These results add new activities to the list of those exerted by PR-3 and indicate a differential inhibition as a result of EGCG.

Key Words: neutrophils • gelatinolysis • EGCG