Cysteine protease cathepsin X modulates immune response via activation of beta2 integrins.
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 beta2 subunit. Here its potential role in regulating lymphocyte proliferation via Mac-1 and the other beta2 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 alpha(L)-mCFP and beta2-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 beta2 integrin receptors, LFA-1 and Mac-1, which exhibit opposing roles in lymphocyte activation.
Obermajer
Natasa
N
Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Repnik
Urska
U
Jevnikar
Zala
Z
Turk
Boris
B
Kreft
Marko
M
Kos
Janko
J
D018821:CD18 Antigens / Q000378:metabolism*; D002449:Cell Aggregation / Q000276:immunology; D049109:Cell Proliferation; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D010835:Phytohemagglutinins