title: Tailor-made inflammation: how neutrophil serine proteases modulate the inflammatory response.
abstract: Neutrophil granulocytes are important mediators of innate immunity, but also participate in the pathogenesis of (auto)inflammatory diseases. Neutrophils express a specific set of proteolytic enzymes, the neutrophil serine proteases (NSPs), which are stored in cytoplasmic granules and can be secreted into the extra- and pericellular space upon cellular activation. These NSPs, namely cathepsin G (CG), neutrophil elastase (NE), and proteinase 3 (PR3), have early been implicated in bacterial defense. However, NSPs also regulate the inflammatory response by specifically altering the function of cytokines and chemokines. For instance, PR3 and NE both inactivate the anti-inflammatory mediator progranulin, which may play a role in chronic inflammation. Here, we provide a concise update on NSPs as modulators of inflammation and discuss the biological and pathological significance of this novel function of NSPs. Mounting evidence support an important proinflammatory function for PR3, which may have been underestimated in the past.
authors.affiliation: Department of Anatomy, University of California, 513 Parnassus Avenue, San Francisco, CA 94143-0452, USA. kai.kessenbrock@ucsf.edu
authors.forename: Kai
authors.initials: K
authors.lastname: Kessenbrock
authors.forename: Therese
authors.initials: T
authors.lastname: Dau
authors.forename: Dieter E
authors.initials: DE
authors.lastname: Jenne
mesh_terms: D018925:Chemokines / Q000276:immunology; D007249:Inflammation / Q000201:enzymology*; D009504:Neutrophils / Q000201:enzymology*; D011956:Receptors, Cell Surface / Q000276:immunology; D057057:Serine Proteases / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018925:Chemokines; D011956:Receptors, Cell Surface; D057057:Serine Proteases
references.citation: J Immunol. 1995 Aug 15;155(4):2158-64
references.pmid: 7636264
references.citation: Lancet. 2005 Jun 25-Jul 1;365(9478):2225-36
references.pmid: 15978931
references.citation: Science. 2004 Mar 5;303(5663):1532-5
references.pmid: 15001782
references.citation: Immunity. 2005 Jun;22(6):679-91
references.pmid: 15963783
references.citation: J Clin Invest. 2002 Feb;109(3):363-71
references.pmid: 11827996
references.citation: Clin Exp Immunol. 2009 May;156(2):336-43
references.pmid: 19292764
references.citation: BMB Rep. 2008 Nov 30;41(11):814-9
references.pmid: 19017495
references.citation: FEBS Lett. 2003 Jun 5;544(1-3):129-32
references.pmid: 12782302
references.citation: J Clin Invest. 1980 Nov;66(5):987-95
references.pmid: 6253528
references.citation: Nat Rev Immunol. 2006 Mar;6(3):173-82
references.pmid: 16498448
references.citation: Proc Natl Acad Sci U S A. 1999 May 25;96(11):6261-6
references.pmid: 10339575
references.citation: Biochim Biophys Acta. 2010 Jul-Aug;1802(7-8):649-58
references.pmid: 20438838
references.citation: J Mol Med (Berl). 2003 Oct;81(10):600-12
references.pmid: 12928786
references.citation: Nature. 1997 Feb 20;385(6618):729-33
references.pmid: 9034190
references.citation: J Leukoc Biol. 2001 Feb;69(2):197-206
references.pmid: 11272269
references.citation: J Clin Invest. 2008 Jul;118(7):2438-47
references.pmid: 18568075
references.citation: Pharmacol Ther. 2008 Nov;120(2):197-217
references.pmid: 18793669
references.citation: FEBS Lett. 1994 Sep 26;352(2):231-5
references.pmid: 7925979
references.citation: Nat Rev Immunol. 2006 Jul;6(7):541-50
references.pmid: 16799473
references.citation: J Immunol. 2003 Jun 1;170(11):5690-6
references.pmid: 12759451
references.citation: J Exp Med. 2010 Jan 18;207(1):117-28
references.pmid: 20026663
references.citation: Trends Genet. 2008 Apr;24(4):186-94
references.pmid: 18328591
references.citation: Cell. 2000 Sep 1;102(5):647-55
references.pmid: 11007483
references.citation: Arthritis Rheum. 2009 Dec;60(12):3651-62
references.pmid: 19950280
references.citation: Annu Rev Immunol. 2005;23:197-223
references.pmid: 15771570
references.citation: Am J Respir Cell Mol Biol. 2004 Apr;30(4):576-84
references.pmid: 14565940
references.citation: Cell. 2002 Dec 13;111(6):867-78
references.pmid: 12526812
references.citation: J Immunol. 2001 Dec 1;167(11):6568-75
references.pmid: 11714826
references.citation: J Immunol. 2008 Oct 15;181(8):5702-10
references.pmid: 18832729
references.citation: J Exp Med. 2004 Sep 20;200(6):713-24
references.pmid: 15381727
references.citation: Nat Med. 2009 Jun;15(6):623-5
references.pmid: 19448636
references.citation: J Immunol. 2004 Apr 1;172(7):4493-502
references.pmid: 15034066
references.citation: J Immunol. 2000 Sep 15;165(6):3366-74
references.pmid: 10975855