Abstract
The cysteine protease dipeptidyl peptidase I (DPPI) activates granule-associated immune-cell serine proteases. The in vivo activator of DPPI itself is unknown; however, cathepsins L and S are candidates because they activate pro-DPPI in vitro. In this study, we tested whether cathepsins L and S activate pro-DPPI in vivo by characterizing DPPI activity and processing in cells lacking cathepsins L and S. DPPI activity, and the relative size and amounts of DPPI heavy and light chains, were identical in mast cells from wild-type and cathepsin L/S double-null mice. Furthermore, the activity of DPPI-dependent chymase was preserved in tissues of cathepsin L/S double-null mice. These results show that neither cathepsin L nor S is required for activation of DPPI and suggest that one or more additional proteases is responsible.
References
Adkison, A.M., Raptis, S.Z., Kelley, D.G., and Pham, C.T. (2002). Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis. J. Clin. Invest.109, 363–371.10.1172/JCI0213462Search in Google Scholar
Dahl, S.W., Halkier, T., Lauritzen, C., Dolenc, I., Pedersen, J., Turk, V., and Turk, B. (2001). Human recombinant pro-dipeptidyl peptidase I (cathepsin C) can be activated by cathepsins L and S but not by autocatalytic processing. Biochemistry40, 1671–1678.10.1021/bi001693zSearch in Google Scholar PubMed
Dolenc, I., Turk, B., Pungercic, G., Ritonja, A., and Turk, V. (1995). Oligomeric structure and substrate induced inhibition of human cathepsin C. J. Biol. Chem.270, 21626–21631.10.1074/jbc.270.37.21626Search in Google Scholar PubMed
Hart, T.C., Hart, P.S., Bowden, D.W., Michalec, M.D., Callison, S.A., Walker, S.J., Zhang, Y., and Firatli, E. (1999). Mutations of the cathepsin C gene are responsible for Papillon-Lefèvre syndrome. J. Med. Genet.36, 881–887.10.1136/jmg.36.12.881Search in Google Scholar
Leder, L.D. (1979). The chloroacetate esterase reaction. A useful means of histological diagnosis of hematological disorders from paraffin sections of skin. Am. J. Dermatopathol.1, 39–42.10.1097/00000372-197901010-00005Search in Google Scholar
Liu, J., Sukhova, G.K., Yang, J.T., Sun, J., Ma, L., Ren, A., Xu, W.H., Fu, H., Dolganov, G.M., Hu, C., et al. (2006). Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells. Atherosclerosis184, 302–311.10.1016/j.atherosclerosis.2005.05.012Search in Google Scholar PubMed
Mallen-St. Clair, J., Pham, C.T.N., Villalta, S.A., Caughey, G.H., and Wolters, P.J. (2004). Mast cell dipeptidyl peptidase I mediates survival from sepsis. J. Clin. Invest.113, 628–634.10.1172/JCI200419062Search in Google Scholar
McCoy, K., Gal, S., Schwartz, R.H., and Gottesman, M.M. (1988). An acid protease secreted by transformed cells interferes with antigen processing. J. Cell Biol.106, 1879–1884.10.1083/jcb.106.6.1879Search in Google Scholar PubMed PubMed Central
McQueney, M.S., Amegadzie, B.Y., D'Alessio, K., Hanning, C.R., McLaughlin, M.M., McNulty, D., Carr, S.A., Ijames, C., Kurdyla, J., and Jones, C.S. (1997). Autocatalytic activation of human cathepsin K. J. Biol. Chem.272, 13955–13960.10.1074/jbc.272.21.13955Search in Google Scholar PubMed
Menard, R., Carmona, E., Takebe, S., Dufour, E., Plouffe, C., Mason, P., and Mort, J.S. (1998). Autocatalytic processing of recombinant human procathepsin L. Contribution of both intermolecular and unimolecular events in the processing of procathepsin L in vitro. J. Biol. Chem.273, 4478–4484.10.1074/jbc.273.8.4478Search in Google Scholar PubMed
Pham, C.T. and Ley, T.J. (1999). Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc. Natl. Acad. Sci. USA96, 8627–8632.10.1073/pnas.96.15.8627Search in Google Scholar PubMed PubMed Central
Potts, W., Bowyer, J., Jones, H., Tucker, D., Freemont, A.J., Millest, A., Martin, C., Vernon, W., Neerunjun, D., Slynn, G., et al. (2004). Cathepsin L-deficient mice exhibit abnormal skin and bone development and show increased resistance to osteoporosis following ovariectomy. Int. J. Exp. Pathol.85, 85–96.10.1111/j.0959-9673.2004.00373.xSearch in Google Scholar
Razin, E., Ihle, J.N., Seldin, D., Mencia-Huerta, J.M., Katz, H.R., LeBlanc, P.A., Hein, A., Caulfield, J.P., Austen, K.F., and Stevens, R.L. (1984). Interleukin 3: a differentiation and growth factor for the mouse mast cell that contains chondroitin sulfate E proteoglycan. J. Immunol.132, 1479–1486.10.4049/jimmunol.132.3.1479Search in Google Scholar
Shi, G.P., Munger, J.S., Meara, J.P., Rich, D.H., and Chapman, H.A. (1992). Molecular cloning and expression of human alveolar macrophage cathepsin S, an elastinolytic cysteine protease. J. Biol. Chem.267, 7258–7262.10.1016/S0021-9258(18)42513-6Search in Google Scholar
Shi, G.P., Villadangos, J.A., Dranoff, G., Small, C., Gu, L., Haley, K.J., Riese, R., Ploegh, H.L., and Chapman, H.A. (1999). Cathepsin S required for normal MHC class II peptide loading and germinal center development. Immunity10, 197–206.10.1016/S1074-7613(00)80020-5Search in Google Scholar
Toomes, C., James, J., Wood, A.J., Wu, C.L., McCormick, D., Lench, N., Hewitt, C., Moynihan, L., Roberts, E., Woods, C.G., et al. (1999). Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Nat. Genet.23, 421–424.10.1038/70525Search in Google Scholar PubMed
Turk, B., Turk, V., and Turk, D. (1997). Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors. Biol. Chem.378, 141–150.Search in Google Scholar
Turk, D., Janjic, V., Stern, I., Podobnik, M., Lamba, D., Dahl, S.W., Lauritzen, C., Pedersen, J., Turk, V., and Turk, B. (2001). Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. EMBO J.20, 6570–6582.10.1093/emboj/20.23.6570Search in Google Scholar PubMed PubMed Central
Vasiljeva, O., Dolinar, M., Pungercar, J.R., Turk, V., and Turk, B. (2005). Recombinant human procathepsin S is capable of autocatalytic processing at neutral pH in the presence of glycosaminoglycans. FEBS Lett.579, 1285–1290.10.1016/j.febslet.2004.12.093Search in Google Scholar PubMed
Wolters, P.J., Raymond, W.W., Blount, J.L., and Caughey, G.H. (1998). Regulated expression, processing, and secretion of dog mast cell dipeptidyl peptidase I. J. Biol. Chem.273, 15514–15520.10.1074/jbc.273.25.15514Search in Google Scholar PubMed
Wolters, P.J., Pham, C.T., Muilenburg, D.J., Ley, T.J., and Caughey, G.H. (2001). Dipeptidyl peptidase I is essential for activation of mast cell chymases, but not tryptases, in mice. J. Biol. Chem.276, 18551–18556.10.1074/jbc.M100223200Search in Google Scholar PubMed
©2006 by Walter de Gruyter Berlin New York