PMID:15034066

Citation	Young, RE, Thompson, RD, Larbi, KY, La, M, Roberts, CE, Shapiro, SD, Perretti, M and Nourshargh, S (2004) Neutrophil elastase (NE)-deficient mice demonstrate a nonredundant role for NE in neutrophil migration, generation of proinflammatory mediators, and phagocytosis in response to zymosan particles in vivo. J. Immunol. 172:4493-502
Abstract	Neutrophil elastase (NE) remains a controversial player in the process of leukocyte transmigration and much of this controversy stems from conflicting reports on the effects of NE inhibitors. The availability of NE-deficient mice (NE(-/-)) provides a clean and elegant tool for the study of leukocyte migration in vivo. In this study, NE(-/-) mice were used to investigate the role of NE in leukocyte migration through cremasteric venules, as observed by intravital microscopy, induced by locally administered cytokines IL-1beta and TNF-alpha and the particulate stimulus, zymosan. Although no defects in leukocyte responses induced by the cytokines were observed, zymosan-induced leukocyte firm adhesion and transmigration was suppressed in NE(-/-) mice. These responses were also inhibited in wild-type mice when zymosan was coinjected with a specific NE inhibitor. Quantification of inflammatory mediator levels in homogenates of zymosan-stimulated tissues indicated reductions in levels of IL-1beta, KC, and macrophage inflammatory protein-1alpha in NE(-/-) mice. Furthermore, phagocytosis of fluorescent zymosan particles, as observed by intravital microscopy, was diminished in NE-deficient animals. Collectively, the findings of this study indicate a nonredundant role for NE in zymosan-induced leukocyte firm adhesion and transmigration, and that this defect is associated with impaired generation of proinflammatory mediators as well as phagocytosis of zymosan particles in vivo.
Links	PubMed
Keywords	Animals; Cell Adhesion Molecules/biosynthesis; Inflammation Mediators/antagonists & inhibitors; Inflammation Mediators/metabolism; Interleukin-1/pharmacology; Leukocyte Elastase/deficiency; Leukocyte Elastase/genetics; Leukocyte Elastase/physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Video; Muscle, Skeletal/blood supply; Neutrophil Infiltration/genetics; Neutrophil Infiltration/immunology; Neutrophils/enzymology; Neutrophils/immunology; Peritoneal Cavity/cytology; Phagocytosis/genetics; Phagocytosis/immunology; Scrotum; Tumor Necrosis Factor-alpha/pharmacology; Venules/cytology; Venules/immunology; Zymosan/administration & dosage
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