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Cysteine protease cathepsin X modulates immune response via activation of β 2 integrins
Author(s) -
Obermajer Nataša,
Repnik Urška,
Jevnikar Zala,
Turk Boris,
Kreft Marko,
Kos Janko
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02740.x
Subject(s) - cathepsin , lymphocyte function associated antigen 1 , cathepsin s , microbiology and biotechnology , integrin , biology , cathepsin b , cathepsin d , cathepsin l , integrin alpha m , chemistry , receptor , biochemistry , flow cytometry , enzyme
Summary Cathepsin X is a lysosomal, cysteine dependent carboxypeptidase. Its expression is restricted to cells of the immune system, suggesting a function related to the processes of inflammatory and immune responses. It has been shown to stimulate macrophage antigen‐1 (Mac‐1) receptor‐dependent adhesion and phagocytosis via interaction with integrin β 2 subunit. Here its potential role in regulating lymphocyte proliferation via Mac‐1 and the other β 2 integrin receptor, lymphocyte function‐associated antigen‐1 (LFA‐1) has been investigated. Cathepsin X has been shown to suppress proliferation of human peripheral blood mononuclear cells, by activation of Mac‐1, known as a suppressive factor for lymphocyte proliferation. On the other hand, co‐localization of cathepsin X and LFA‐1 supports the role of cathepsin X in regulating LFA‐1 activity, which enhances lymphocyte proliferation. As shown by fluorescence resonance energy transfer, using U‐937 and Jurkat cells transfected with α L ‐mCFP and β 2 ‐mYFP, recombinant cathepsin X directly activates LFA‐1. The activation was confirmed by increased binding of monoclonal antibody 24, recognizing active LFA‐1. We demonstrate that cathepsin X is involved in the regulation of two β 2 integrin receptors, LFA‐1 and Mac‐1, which exhibit opposing roles in lymphocyte activation.