Role of cathepsin C in elastase-induced mouse abdominal aortic aneurysms

Evaluation of: Pagano MB, Bartoli MA, Ennis TL et al.: Critical role of dipeptidyl peptidase I in neutrophil recruitment during the development of experimental abdominal aortic aneurysms. Proc. Natl Acad. Sci. USA 104(8), 2855-2860 (2007). In this study, the authors used dipeptidyl peptidase I (DPPI) gene-targeted mice and an aortic elastase perfusion-induced mouse abdominal aortic aneurysm (AAA) model to examine the role of DPPI, also termed cathepsin C, in the development of AAA. Mice lacking this protease are resistant to AAA formation. Interestingly, these authors found that DPPI activity controls neutrophil recruitment to the sites of inflammation, specifically AAA lesions in this case. By producing chemokine CXCL2, neutrophils in AAA lesions recruit additional neutrophils to the lesion sites where these cells utilize DPPI to activate neutrophil serine proteases, including neutrophil elastase, cathepsin G and proteinase 3, which may be further used to stimulate macrophage cytokine and chemokine production. In addition to DPPI-deficient mice, the authors also used antibodies against neutrophils (Gr-1) or CXCL2 receptor, CXCR2, to deplete neutrophils or to block the action of neutrophil chemokines to affirm their hypothesis.