Neutrophil serine proteases: Specific regulators of inflammation

Nature Reviews Immunology

Volumn 6, Issue 7, 2006, Pages 541-550

  Pham, Christine T N ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AZUROCIDIN; CATHELICIDIN; CATHEPSIN G; CD11B ANTIGEN; CD14 ANTIGEN; CD16 ANTIGEN; CD18 ANTIGEN; CHEMOKINE; CHYMASE; COLLAGENASE; CYTOCHROME B558; CYTOKINE; DEFENSIN; ENZYME PRECURSOR; FORMYLPEPTIDE RECEPTOR; G PROTEIN COUPLED RECEPTOR; GELATINASE; LACTOFERRIN; LEUKOCYTE ELASTASE; LYSOZYME; MYELOBLASTIN; MYELOPEROXIDASE; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 1; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SERINE PROTEINASE; SERINE PROTEINASE INHIBITOR; SNARE PROTEIN; TRYPTASE; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME;

ARTHRITIS; BACTERICIDAL ACTIVITY; BEIGE MOUSE; CALCIUM TRANSPORT; CHEDIAK HIGASHI SYNDROME; CHROMOSOME 14; COLLAGEN INDUCED ARTHRITIS; CYTOKINE PRODUCTION; ESCHERICHIA COLI; EXOCYTOSIS; HOST RESISTANCE; IMMUNE COMPLEX NEPHRITIS; INFLAMMATION; INTRACELLULAR KILLING; KERATOSIS PALMOPLANTARIS; KLEBSIELLA PNEUMONIAE; MOUSE; MOUSE STRAIN; NEUTROPENIA; NEUTROPHIL; NEUTROPHIL GRANULE; NONHUMAN; PEMPHIGOID; PHAGOCYTOSIS; PHAGOLYSOSOME; PRIORITY JOURNAL; PROMYELOCYTIC LEUKEMIA; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; PROTEINURIA; RESPIRATORY BURST; REVIEW; SALMONELLA ENTERICA; SHIGELLA FLEXNERI; STAPHYLOCOCCUS AUREUS; SYSTEMATIC REVIEW; WEGENER GRANULOMATOSIS; YERSINIA ENTEROCOLITICA;

ANIMALS; HUMANS; INFECTION; INFLAMMATION; MICE; MODELS, IMMUNOLOGICAL; NEUTROPHILS; SERINE ENDOPEPTIDASES;

EID: 33745559712     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri1841     Document Type: Review

References (104)

1. Dinauer, M. C., Lekstrom-Himes, J. A. & Dale, D. C. Inherited neutrophil disorders: molecular basis and new therapies. Hematology (Am. Soc. Hematol. Educ. Program), 303-318 (2000).
2. Faurschou, M. & Borregaard, N. Neutrophil granules and secretory vesicles in inflammation. Microbes Infect 5, 1317-1327 (2003).
3. Belaaouaj, A. et al. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nature Med. 4, 615-618 (1998). The first study to show that mice deficient in neutrophil elastase are more susceptible to infection with Gram-negative bacteria than wild-type mice.
4. + flux. Nature 416, 291-297 (2002). This paper provides a new working model that features neutrophil serine proteases, not ROS, as the main agents responsible for the intracellular killing of bacteria.
5. Tkalcevic, J. et al. Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G. Immunity 12, 201-210 (2000). This study shows that, compared with wild-type mice, mice deficient in cathepsin G and neutrophil elastase are more susceptible to certain fungal infections but more resistant to LPS-induced septic shock.
6. Schrijver, G., Schalkwijk, J., Robben, J. C., Assmann, K. J. & Koene, R. A. Antiglomerular basement membrane nephritis in beige mice. Deficiency of leukocytic neutral proteinases prevents the induction of albuminuria in the heterologous phase. J. Exp. Med. 169, 1435-1448 (1989).
7. Liu, Z. et al. A critical role for neutrophil elastase in experimental bullous pemphigoid. J. Clin. Invest. 105, 113-123 (2000).
8. Adkison, A. M., Raptis, S. Z., Kelley, D. G. & Pham, C. T. Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis. J. Clin. Invest. 109, 363-371 (2002). This paper shows that the in vivo production of the pro-inflammatory cytokines TNF and IL-1β is reduced in mice lacking DPPI or neutrophil elastase and cathepsin G.
9. Hu, Y. & Pham, C. T. Dipeptidyl peptidase I regulates the development of collagen-induced arthritis. Arthritis Rheum. 52, 2553-2558 (2005).
10. Shiflett, S. L., Kaplan, J. & Ward, D. M. Chediak-Higashi Syndrome: a rare disorder of lysosomes and lysosome related organelles. Pigment Cell Res. 15, 251-257 (2002).
11. Owen, C. A., Campbell, M. A., Sannes, P. L., Boukedes, S. S. & Campbell, E. J. Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases. J. Cell Biol. 131, 775-789 (1995). This paper shows that neutrophil elastase and cathepsin G remain bound to the cell surface after release and that they escape inhibition by endogenous inhibitors.
12. Campbell, E. J., Campbell, M. A. & Owen, C. A. Bioactive proteinase 3 on the cell surface of human neutrophils: quantification, catalytic activity, and susceptibility to inhibition. J. Immunol. 165, 3366-3374 (2000).
13. Zimmer, M. et al. Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter. Proc. Natl Acad. Sci. USA 89, 8215-8219 (1992).
14. Belaaouaj, A., Walsh, B. C., Jenkins, N. A., Copeland, N. G. & Shapiro, S. D. Characterization of the mouse neutrophil elastase gene and localization to chromosome 10. Mamm. Genome 8, 5-8 (1997).
15. Gabay, J. E. et al. Antibiotic proteins of human polymorphonuclear leukocytes. Proc. Natl Acad. Sci. USA 86, 5610-5614 (1989).
16. Chertov, O. et al. Identification of human neutrophil-derived cathepsin G and azurocidin/CAP37 as chemoattractants for mononuclear cells and neutrophils. J. Exp. Med. 186, 739-747 (1997).
17. Caughey, G. H. et al. The human mast cell chymase gene (CMA1): mapping to the cathepsin G/granzyme gene cluster and lineage-restricted expression. Genomics 15, 614-620 (1993).
18. Heusel, J. W. et al. Molecular cloning, chromosomal location, and tissue-specific expression of the murine cathepsin G gene. Blood 81, 1614-1623 (1993).
19. Garwicz, D., Lennartsson, A., Jacobsen, S. E., Gullberg, U. & Lindmark, A. Biosynthetic profiles of neutrophil serine proteases in a human bone marrow-derived cellular myeloid differentiation model. Haematologica 90, 38-44 (2005).
20. Shapiro, S. D., Campbell, E. J., Senior, R. M. & Welgus, H. G. Proteinases secreted by human mononuclear phagocytes. J. Rheumatol. 27 (Suppl.), 95-98 (1991).
21. Mayet, W. J., Csernok, E., Szymkowiak, C., Gross, W. L. & Meyer zum Buschenfelde, K. H. Human endothelial cells express proteinase 3, the target antigen of anticytoplasmic antibodies in Wegener's granulomatosis. Blood 82, 1221-1229 (1993).
22. Schwarting, A. et al. Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener's granulomatosis. Kidney Int. 57, 2412-2422 (2000).
23. Brockmann, H. et al. Proteinase-3 as the major autoantigen of c-ANCA is strongly expressed in lung tissue of patients with Wegener's granulomatosis. Arthritis Res. 4, 220-225 (2002).
24. Pham, C. T. & Ley, T. J. Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc. Natl Acad. Sci. USA 96, 8627-8632 (1999).
25. Wolters, P. J., Pham, C. T., Muilenburg, D. J., Ley, T. J. & Caughey, G. H. Dipeptidyl peptidase I is essential for activation of mast cell chymases, but not tryptases, in mice. J. Biol. Chem. 276, 18551-18556 (2001).
26. Garwicz, D., Lindmark, A., Persson, A. M. & Gullberg, U. On the role of the proform-conformation for processing and intracellular sorting of human cathepsin G. Blood 92, 1415-1422 (1998).
27. Salvesen, G. & Enghild, J. J. An unusual specificity in the activation of neutrophil serine proteinase zymogens. Biochemistry 29, 5304-5308 (1990).
28. Rao, N. V., Rao, G. V., Marshall, B. C. & Hoidal, J. R. Biosynthesis and processing of proteinase 3 in U937 cells. Processing pathways are distinct from those of cathepsin G. J. Biol. Chem. 271, 2972-2978 (1996).
29. Gullberg, U. et al. Carboxyl-terminal prodomain-deleted human leukocyte elastase and cathepsin G are efficiently targeted to granules and enzymatically activated in the rat basophilic/mast cell line RBL. J. Biol. Chem. 270, 12912-12918 (1995).
30. Horwitz, M., Benson, K. F., Duan, Z., Li, F. Q. & Person, R. E. Hereditary neutropenia: dogs explain human neutrophil elastase mutations. Trends Mol. Med. 10, 163-170 (2004).
31. Benson, K. F. et al. Mutations associated with neutropenia in dogs and humans disrupt intracellular transport of neutrophil elastase. Nature Genet. 35, 90-96 (2003).
32. Niemann, C. U. et al. Localization of serglycin in human neutrophil granulocytes and their precursors. J. Leukoc. Biol. 76, 406-415 (2004).
33. Salaun, C., James, D. J., Greaves, J. & Chamberlain, L. H. Plasma membrane targeting of exocytic SNARE proteins. Biochim. Biophys. Acta 1693, 81-89 (2004).
34. Brumell, J. H. et al. Subcellular distribution of docking/fusion proteins in neutrophils, secretory cells with multiple exocytic compartments. J. Immunol. 155, 5750-5759 (1995).
35. Nabokina, S., Egea, C., Blasi, J. & Mollinedo, F. Intracellular location of SNAP-25 in human neutrophils. Biochem. Biophys. Res. Commun. 239, 592-597 (1997).
36. Martin-Martin, B., Nabokina, S. M., Blasi, J., Lazo, P. A. & Mollinedo, F. Involvement of SNAP-23 and syntaxin 6 in human neutrophil exocytosis. Blood 96, 2574-2583 (2000).
37. Rest, R. F. Human neutrophil and mast cell proteases implicated in inflammation. Methods Enzymol. 163, 309-327 (1988).
38. Williams, S. E., Brown, T. I., Roghanian, A. & Sallenave, J. M. SLPI and elafin: one glove, many fingers. Clin. Sci. (Lond.) 110, 21-35 (2006).
39. Huntington, J. A., Read, R. J. & Carrell, R. W. Structure of a serpin-protease complex shows inhibition by deformation. Nature 407, 923-926 (2000).
40. Liu, Z. et al. The serpin α1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo. Cell 102, 647-655 (2000).
41. Churg, A. et al. α1-antitrypsin and a broad spectrum metalloprotease inhibitor, RS113456, have similar acute anti-inflammatory effects. Lab. Invest. 81, 1119-1131 (2001).
42. Senior, R. M., Griffin, G. L. & Mecham, R. P. Chemotactic activity of elastin-derived peptides. J. Clin. Invest. 66, 859-862 (1980).
43. Weinrauch, Y., Drujan, D., Shapiro, S. D., Weiss, J. & Zychlinsky, A. Neutrophil elastase targets virulence factors of enterobacteria. Nature 417, 91-94 (2002).
44. Shafer, W. M., Hubalek, F., Huang, M. & Pohl, J. Bactericidal activity of a synthetic peptide (CG 117-136) of human lysosomal cathepsin G is dependent on arginine content. Infect. Immun. 64, 4842-4845 (1996).
45. Shafer, W. M. et al. Tailoring an antibacterial peptide of human lysosomal cathepsin G to enhance its broad-spectrum action against antibiotic-resistant bacterial pathogens. Curr. Pharm. Des. 8, 695-702 (2002).
46. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389-395 (2002).
47. Belaaouaj, A., Kim, K. S. & Shapiro, S. D. Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase. Science 289, 1185-1188 (2000).
48. Hirche, T. O., Gaut, J. P., Heinecke, J. W. & Belaaouaj, A. Myeloperoxidase plays critical roles in killing Klebsiella pneumoniae and inactivating neutrophil elastase: effects on host defense. J. Immunol. 174, 1557-1565 (2005).
49. Pham, C. T., Ivanovich, J. L., Raptis, S. Z., Zehnbauer, B. & Ley, T. J. Papillon-Lefevre syndrome: correlating the molecular, cellular, and clinical consequences of cathepsin C/dipeptidyl peptidase I deficiency in humans. J. Immunol. 173, 7277-7281 (2004).
50. Brinkmann, V. et al. Neutrophil extracellular traps kill bacteria. Science 303, 1532-1535 (2004).
51. Sorensen, O. E. et al. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 97, 3951-3959 (2001).
52. Lopez-Boado, Y. S., Espinola, M., Bahr, S. & Belaaouaj, A. Neutrophil serine proteinases cleave bacterial flagellin, abrogating its host response-inducing activity. J. Immunol. 172, 509-515 (2004).
53. Owen, C. A. & Campbell, E. J. The cell biology of leukocyte-mediated proteolysis. J. Leukoc. Biol. 65, 137-150 (1999).
54. Cai, T. Q. & Wright, S. D. Human leukocyte elastase is an endogenous ligand for the integrin CR3 (CD11b/CD18, Mac-1, αMβ2) and modulates polymorphonuclear leukocyte adhesion. J. Exp. Med. 184, 1213-1223 (1996).
55. David, A., Kacher, Y., Specks, U. & Aviram, I. Interaction of proteinase 3 with CD11b/CD18 (β2 integrin) on the cell membrane of human neutrophils. J. Leukoc. Biol. 74, 551-557 (2003).
56. David, A., Fridlich, R. & Aviram, I. The presence of membrane proteinase 3 in neutrophil lipid rafts and its colocalization with FcγRIIIb and cytochrome b558. Exp. Cell Res. 308, 156-165 (2005).
57. Kurschus, F. C., Bruno, R., Fellows, E., Falk, C. S. & Jenne, D. E. Membrane receptors are not required to deliver granzyme B during killer cell attack. Blood 105, 2049-2058 (2005).
58. Carden, D. L. & Korthuis, R. J. Protease inhibition attenuates microvascular dysfunction in postischemic skeletal muscle. Am. J. Physiol. 271, H1947-52 (1996).
59. Kawabata, K. et al. Delayed neutrophil elastase inhibition prevents subsequent progression of acute lung injury induced by endotoxin inhalation in hamsters. Am. J. Respir. Crit Care Med. 161, 2013-2018 (2000).
60. Kakimoto, K., Matsukawa, A., Yoshinaga, M. & Nakamura, H. Suppressive effect of a neutrophil elastase inhibitor on the development of collagen-induced arthritis. Cell. Immunol. 165, 26-32 (1995).
61. Padrines, M., Wolf, M., Walz, A. & Baggiolini, M. Interleukin-8 processing by neutrophil elastase, cathepsin G and proteinase-3. FEBS Lett. 352, 231-235 (1994).
62. Nufer, O., Corbett, M. & Walz, A. Amino-terminal processing of chemokine ENA-78 regulates biological activity. Biochemistry 38, 636-642 (1999).
63. Berahovich, R. D. et al. Proteolytic activation of alternative CCRI ligands in inflammation. J. Immunol. 174, 7341-7351 (2005).
64. Wittamer, V. et al. Neutrophil-mediated maturation of chemerin: a link between innate and adaptive immunity. J. Immunol. 175, 487-493 (2005).
65. Rao, R. M. et al. Elastase release by transmigrating neutrophils deactivates endothelial-bound SDF-1α and attenuates subsequent T lymphocyte transendothelial migration. J. Exp. Med. 200, 713-724 (2004).
66. Ryu, O. H. et al. Proteolysis of macrophage inflammatory protein-1α isoforms LD78β and LD78α by neutrophil-derived serine proteases. J. Biol. Chem. 280, 17415-17421 (2005).
67. Black, R. A. et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells. Nature 385, 729-733 (1997).
68. Thornberry, N. A. et al. A novel heterodimeric cysteine protease is required for interleukin-1β processing in monocytes. Nature 356, 768-774 (1992).
69. Robache-Gallea, S. et al. In vitro processing of human tumor necrosis factor-α. J. Biol. Chem. 270, 23688-23692 (1995).
70. Coeshott, C. et al. Converting enzyme-independent release of tumor necrosis factor α and IL-1β from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3. Proc. Natl Acad. Sci. USA 96, 6261-6266 (1999).
71. Scuderi, P., Nez, P. A., Duerr, M. L., Wong, B. J. & Valdez, C. M. Cathepsin-G and leukocyte elastase inactivate human tumor necrosis factor and lymphotoxin. Cell. Immunol. 135, 299-313 (1991).
72. Bank, U., Kupper, B., Reinhold, D., Hoffmann, T. & Ansorge, S. Evidence for a crucial role of neutrophil-derived serine proteases in the inactivation of interleukin-6 at sites of inflammation. FEBS Lett. 461, 235-240 (1999).
73. Young, R. E. et al. 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, 4493-4502 (2004). This paper shows that mice deficient in neutrophil elastase have a defect in neutrophil recruitment and cytokine production in vivo when challenged with zymosan.
74. DeMali, K. A., Wennerberg, K. & Burridge, K. Integrin signaling to the actin cytoskeleton. Curr. Opin. Cell Biol. 15, 572-582 (2003).
75. Raptis, S. Z., Shapiro, S. D., Simmons, P. M., Cheng, A. M. & Pham, C. T. Serine protease cathepsin G regulates adhesion-dependent neutrophil effector functions by modulating integrin clustering. Immunity 22, 679-691 (2005). This paper shows that cathepsin G regulates neutrophil functions by modulating cellular activation and cytoskeletal rearrangement.
76. IIb subunit heavy chain. Involvement in the potentiation of platelet aggregation. J. Biol. Chem. 272, 11636-11647 (1997).
77. Coughlin, S. R. & Camerer, E. PARticipation in inflammation. J. Clin. Invest. 111, 25-27 (2003).
78. Sambrano, G. R. et al. Cathepsin G activates protease-activated receptor-4 in human platelets. J. Biol. Chem. 275, 6819-6823 (2000).
79. Loew, D. et al. Proteolysis of the exodomain of recombinant protease-activated receptors: prediction of receptor activation or inactivation by MALDI mass spectrometry. Biochemistry 39, 10812-10822 (2000).
80. Cumashi, A. et al. Neutrophil proteases can inactivate human PAR3 and abolish the co-receptor function of PAR3 on murine platelets. Thromb. Haemost. 85, 533-538 (2001).
81. Uehara, A., Muramoto, K., Takada, H. & Sugawara, S. Neutrophil serine proteinases activate human nonepithelial cells to produce inflammatory cytokines through protease-activated receptor 2. J. Immunol. 170, 5690-5696 (2003). This paper shows that proteinase 3 induces that production of cytokines through PAR2.
82. Uehara, A., Sugawara, Y., Sasano, T., Takada, H. & Sugawara, S. Proinflammatory cytokines induce proteinase 3 as membrane-bound and secretory forms in human oral epithelial cells and antibodies to proteinase 3 activate the cells through protease-activated receptor-2. J. Immunol. 173, 4179-4189 (2004).
83. Walsh, D. E. et al. Interleukin-8 up-regulation by neutrophil elastase is mediated by MyD88/IRAK/TRAF-6 in human bronchial epithelium. J. Biol. Chem. 276, 35494-35499 (2001). This paper shows that neutrophil elastase induces the production of CXCL8 through a TLR4 signalling pathway.
84. Devaney, J. M. et al. Neutrophil elastase up-regulates interleukin-8 via toll-like receptor 4. FEBS Lett. 544, 129-132 (2003).
85. Tsujimoto, H. et al. Neutrophil elastase, MIP-2, and TLR-4 expression during human and experimental sepsis. Shock 23, 39-44 (2005).
86. Brightbill, H. D. et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285, 732-736 (1999).
87. Sun, R. et al. Identification of neutrophil granule protein cathepsin G as a novel chemotactic agonist for the G protein-coupled formyl peptide receptor. J. Immunol. 173, 428-436 (2004). This paper shows that cathepsin C induces monocyte chemotaxis by binding FPR.
88. Fischer, B. M. & Voynow, J. A. Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species. Am. J. Respir. Cell Mol. Biol. 26, 447-452 (2002).
89. Shao, M. X., Ueki, I. F. & Nadel, J. A. Tumor necrosis factor α-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Proc. Natl Acad. Sci. USA 100, 11618-11623 (2003).
90. Shao, M. X. & Nadel, J. A. Neutrophil elastase induces MUC5AC mucin production in human airway epithelial cells via a cascade involving protein kinase C, reactive oxygen species, and TNF-α-converting enzyme. J. Immunol. 175, 4009-4016 (2005).
91. Champagne, B., Tremblay, P., Cantin, A. & St Pierre, Y. Proteolytic cleavage of ICAM-1 by human neutrophil elastase. J. Immunol. 161, 6398-6405 (1998).
92. Levesque, J. P., Takamatsu, Y., Nilsson, S. K., Haylock, D. N. & Simmons, P. J. Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor. Blood 98, 1289-1297 (2001).
93. Ginzberg, H. H. et al. Neutrophil-mediated epithelial injury during transmigration: role of elastase. Am. J. Physiol. Gastrointest Liver Physiol. 281, G705-G717 (2001).
94. Abbott, R. E. et al. Augmented inflammatory responses and altered wound healing in cathepsin G-deficient mice. Arch. Surg. 133, 1002-1006 (1998).
95. Zhu, J. et al. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell 111, 867-878 (2002).
96. Yang, J. J. et al. Internalization of proteinase 3 is concomitant with endothelial cell apoptosis and internalization of myeloperoxidase with generation of intracellular oxidants. Am. J. Pathol. 158, 581-592 (2001).
97. Preston, G. A. et al. Novel effects of neutrophil-derived proteinase 3 and elastase on the vascular endothelium involve in vivo cleavage of NF-κB and proapoptotic changes in JNK, ERK, and p38 MAPK signaling pathways. J. Am. Soc. Nephrol. 13, 2840-2849 (2002).
98. Oltmanns, U., Sukkar, M. B., Xie, S., John, M. & Chung, K. F. Induction of human airway smooth muscle apoptosis by neutrophils and neutrophil elastase. Am. J. Respir. Cell Mol. Biol. 32, 334-341 (2005).
99. Bories, D., Raynal, M. C., Solomon, D. H., Darzynkiewicz, Z. & Cayre, Y. E. Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells. Cell 59, 959-968 (1989).
100. Dublet, B. et al. Cleavage of p21/WAF1/CIP1 by proteinase 3 modulates differentiation of a monocytic cell line. Molecular analysis of the cleavage site. J. Biol. Chem. 280, 30242-30253 (2005).
101. Toomes, C. et al. Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Nature Genet. 23, 421-44 (1999).
102. Lane, A. A. & Ley, T. J. Neutrophil elastase cleaves PML-RARα and is important for the development of acute promyelocytic leukemia in mice. Cell 115, 305-318 (2003).
103. Lane, A. A. & Ley, T. J. Neutrophil elastase is important for PML-retinoic acid receptor α activities in early myeloid cells. Mol. Cell. Biol. 25, 23-33 (2005).
104. Preston, G. A., Yang, J. J., Xiao, H. & Falk, R. J. Understanding the pathogenesis of ANCA: where are we today? Cleve. Clin. J. Med. 69 (Suppl. 2), S1151-S1154 (2002).