Document Detail

Three-dimensional invasion of macrophages is mediated by cysteine cathepsins in protrusive podosomes.
MedLine Citation:
PMID:  23018451     Owner:  NLM     Status:  Publisher    
Podosomes, specialized actin-rich structures in macrophages, degrade the extracellular matrix (ECM) and are involved in cell migration. On two-dimensional surfaces macrophages form spot-like podosomes at the ventral cell surface that develop into protrusive structures in a three-dimensional (3D) environment resembling the ECM. We have shown that the tips of these protrusive podosomes are characterized by increased accumulation of cysteine cathepsins (Cts) B, X, S, H and L, both in human blood macrophages and in human monocytic cell line U-937. Monocyte-to-macrophage differentiation induces an increase in cysteine cathepsin expression and activity, promoting their translocation to the cell surface, where they interact with ECM. This group of proteases is crucial for the extracellular as well as intracellular degradation of ECM, as demonstrated by quantitative monitoring of collagen IV degradation. Furthermore, inhibiting CtsB, X and S significantly impairs macrophage invasion through the 3D matrix. Time-lapse live-cell imaging of CtsB activity revealed that the extracellular and the intracellular ECM degradation are associated with extensive endocytosis at the tip of protrusive podosomes. The targeting of cysteine cathepsins, as the major mediators of human macrophage 3D invasion, could be an approach to the treatment of inflammatory and cancerous diseases.
Zala Jevnikar; Bojana Mirković; Urša Pečar Fonović; Nace Zidar; Urban Svajger; Janko Kos
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-28
Journal Detail:
Title:  European journal of immunology     Volume:  -     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI - 1000, Ljubljana, Slovenia.
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