Neutrophilic Cathepsin C Is Maturated by a Multistep Proteolytic Process and Secreted by Activated Cells during Inflammatory Lung Diseases

摘要: The cysteine protease cathepsin C (CatC) activates granule-associated proinflammatory serine proteases in hematopoietic precursor cells. Its early inhibition the bone marrow is regarded as a new therapeutic strategy for treating proteolysis-driven chronic inflammatory diseases, but its complete elusive vivo. Controlling activity of CatC may be achieved by directly inhibiting with specific inhibitor or/and preventing maturation. We have investigated immunochemically and kinetically occurrence proform human cells differentiated mature immune lung secretions. maturation proCatC obeys multistep mechanism that can entirely managed CatS neutrophilic cell-permeable abrogated release heavy light chains from blocked ∼80% activity. Under these conditions neutrophil proteases, however, was not abolished cell cultures. In patients inflammation, found large amounts sputa. It secreted activated neutrophils confirmed through lipopolysaccharide administration nonhuman primate model. inhibitors currently clinical trials are expected to decrease without affecting those elastase-like proteases.