Cysteine Cathepsins Activate ELR Chemokines and Inactivate Non-ELR Chemokines.

摘要: Cysteine cathepsins are primarily lysosomal proteases involved in general protein turnover, but they also have specific proteolytic functions antigen presentation and bone remodeling. Cathepsins most stable at acidic pH, although growing evidence indicates that physiologically relevant activity neutral pH. Post-translational processing of mature chemokines is a key, yet underappreciated, level chemokine regulation. Although the role selected serine matrix metalloproteases has long been known, little reported about cysteine cathepsins. Here we evaluated cleavage CXC ELR (CXCL1, -2, -3, -5, -8) non-ELR (CXCL9–12) by B, K, L, S pH high resolution Tris-Tricine SDS-PAGE matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Whereas cathepsin B cleaved especially C-terminal region, N terminus with glycosaminoglycans modulating chemokines. The functional consequences cleavages were determined Ca2+ mobilization chemotaxis assays. We show inactivate some cases degrade CXCL9–12. In contrast, specifically process CXCL1, -8 N-terminally to motif, thereby generating agonist forms. This study suggests regulate leukocyte recruitment during protective or pathological inflammation. Background: Chemokine function regulated processing. Results: activate signaling terminate Conclusion: promote inflammation CXCR2-expressing cells. Significance: first comprehensive on