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.