The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin
Open accessAbstract
Neutrophil granulocytes form the body's first line of antibacterial defense, but they also contribute to tissue injury and noninfectious, chronic inflammation. Proteinase 3 (PR3) and neutrophil elastase (NE) are 2 abundant neutrophil serine proteases implicated in antimicrobial defense with overlapping and potentially redundant substrate specificity. Here, we unraveled a cooperative role for PR3 and NE in neutrophil activation and noninfectious inflammation in vivo, which we believe to be novel. Mice lacking both PR3 and NE demonstrated strongly diminished immune complex-mediated (IC-mediated) neutrophil infiltration in vivo as well as reduced activation of isolated neutrophils by ICs in vitro. In contrast, in mice lacking just NE, neutrophil recruitment to ICs was only marginally impaired. The defects in mice lacking both PR3 and NE were directly linked to the accumulation of antiinflammatory progranulin (PGRN). Both PR3 and NE cleaved PGRN in vitro and during neutrophil activation and inflammation in vivo. Local administration of recombinant PGRN potently inhibited neutrophilic inflammation in vivo, demonstrating that PGRN represents a crucial inflammation-suppressing mediator. We conclude that PR3 and NE enhance neutrophil-dependent inflammation by eliminating the local antiinflammatory activity of PGRN. Our results support the use of serine protease inhibitors as antiinflammatory agents.
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Cites
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Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis
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Self-citationConversion of Proepithelin to Epithelins
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Neutrophil Elastase Contributes to Cigarette Smoke-Induced Emphysema in Mice
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Self-citationProgranulin is a mediator of the wound response
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Cited by
Villanueva, E., Yalavarthi, S., Berthier, C. C., Hodgin, J. B., Khandpur, R., Lin, A. M., Rubin, C. J., Zhao, W., Olsen, S. H., Klinker, M., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100450 · Cited by 1,241
Neutrophil Elastase, Proteinase 3, and Cathepsin G as Therapeutic Targets in Human Diseases
Korkmaz, B., Horwitz, M. S., Jenne, D. E., & Gauthier, F. (2010) · Pharmacological Reviews · doi:10.1124/pr.110.002733 · Cited by 870
Self-citationTang, W., Lu, Y., Tian, Q.-Y., Zhang, Y., Guo, F.-J., Liu, G.-Y., Syed, N. M., Lai, Y., Lin, E. A., Kong, L., et al. (2011) · Science · doi:10.1126/science.1199214 · Cited by 761
Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice
Yin, F., Banerjee, R., Thomas, B., Zhou, P., Qian, L., Jia, T., Ma, X., Ma, Y., Iadecola, C., Beal, M. F., et al. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091568 · Cited by 480
Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death
Kambara, H., Liu, F., Zhang, X., Liu, P., Bajrami, B., Teng, Y., Zhao, L., Zhou, S., Yu, H., Zhou, W., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.067 · Cited by 419
Metadata
- Authors
- Kessenbrock, K., Fröhlich, L., Sixt, M., Lämmermann, T., Pfister, H., Bateman, A., Belaaouaj, A., Ring, J., Ollert, M., Fässler, R., & Jenne, D. E.
- Venue
- Journal of Clinical Investigation
- Published
- 2008-06-01
- Volume
- 118
- Issue
- 7
- Pages
- 2438-47
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1998212202
- Cited by
- 366
- References
- 37
- FWCI
- 6.90
- Type
- journal article
- Language
- en
- Open access
- green
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- Kessenbrock, K., Fröhlich, L., Sixt, M., Lämmermann, T., Pfister, H., Bateman, A., Belaaouaj, A., Ring, J., Ollert, M., Fässler, R., & Jenne, D. E. (2008). Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin. Journal of Clinical Investigation. https://doi.org/10.1172/jci34694
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