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 β2 subunit. Here its potential role in regulating lymphocyte proliferation via Mac‐1 and the other β2 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 αL‐mCFP and β2‐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 β2 integrin receptors, LFA‐1 and Mac‐1, which exhibit opposing roles in lymphocyte activation.