Disruption of proprotein convertase 1/3 (PC1/3) expression in mice causes innate immune defects and uncontrolled cytokine secretion

Journal of Biological Chemistry

Volumn 287, Issue 18, 2012, Pages 14703-14717

  Refaie, Sarah ^a   Gagnon, Sandra ^a   Gagnon, Hugo ^a,d   Desjardins, Roxane ^a   D'Anjou, François ^a   D'Orléans Juste, Pedro ^a   Zhu, Xiaorong ^b   Steiner, Donald F ^b   Seidah, Nabil G ^c   Lazure, Claude ^c   Salzet, Michel ^d   Day, Robert ^a,e  

^a UNIVERSITÉ DE SHERBROOKE   (Canada)

^b UNIVERSITY OF CHICAGO   (United States)

^c CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^d UNIV LILLE   (France)

^e Centre Hospitalier Universitaire de Sherbrooke   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMICAL ACTIVATION; CYTOLOGY; IMMUNE SYSTEM; MACROPHAGES; MAMMALS; PHYSIOLOGICAL MODELS;

IMMUNOHISTOCHEMICAL STUDIES; INNATE IMMUNE SYSTEMS; MORPHOLOGICAL FEATURES; NEUROENDOCRINE TISSUES; PERITONEAL MACROPHAGE; PHYSIOLOGICAL FUNCTIONS; POST-TRANSLATIONAL PROCESSING; PRO-INFLAMMATORY CYTOKINES;

THORIUM COMPOUNDS;

INTERLEUKIN 1BETA; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; PROPROTEIN CONVERTASE 1; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL ACTIVATION; CELL STRUCTURE; CONTROLLED STUDY; CYTOKINE RELEASE; CYTOKINE RESPONSE; CYTOKINE STORM; DENDRITIC CELL; DISEASE MARKER; DISEASE PREDISPOSITION; GENE DISRUPTION; GENE EXPRESSION REGULATION; GENETIC ASSOCIATION; IMMUNOHISTOCHEMISTRY; IMMUNOPATHOGENESIS; INNATE IMMUNITY; MOUSE; NONHUMAN; PERITONEUM MACROPHAGE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; SEPTIC SHOCK; SPLENOMEGALY; TH1 CELL; WILD TYPE;

MUS;

EID: 84860364695     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M111.323220     Document Type: Article

References (98)

1. Rholam, M., and Fahy, C. (2009) Processing of peptide and hormone precursors at the dibasic cleavage sites. Cell. Mol. Life Sci. 66, 2075-2091
2. Seidah, N. G., and Chrétien, M. (1999) Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res. 848, 45-62 (Pubitemid 30001653)
3. Hosaka, M., Nagahama, M., Kim, W. S., Watanabe, T., Hatsuzawa, K., Ikemizu, J., Murakami, K., and Nakayama, K. (1991) Arg-X-Lys/Arg-Arg motif as a signal for precursor cleavage catalyzed by furin within the constitutive secretory pathway. J. Biol. Chem. 266, 12127-12130 (Pubitemid 21907065)
4. Seidah, N. G., Khatib, A. M., and Prat, A. (2006) The proprotein convertases and their implication in sterol and/or lipid metabolism. Biol. Chem. 387, 871-877 (Pubitemid 44100233)
5. Siezen, R. J., and Leunissen, J. A. (1997) Subtilases: the superfamily of subtilisin-like serine proteases. Protein Sci. 6, 501-523 (Pubitemid 27120048)
6. Creemers, J. W., Siezen, R. J., Roebroek, A. J., Ayoubi, T. A., Huylebroeck, D., and Van de Ven, W. J. (1993) Modulation of furin-mediated proprotein processing activity by site-directed mutagenesis. J. Biol. Chem. 268, 21826-21834 (Pubitemid 23320684)
7. Creemers, J. W., Vey, M., Schäfer, W., Ayoubi, T. A., Roebroek, A. J., Klenk, H. D., Garten, W., and Van de Ven, W. J. (1995) Endoproteolytic cleavage of its propeptide is a prerequisite for efficient transport of furin out of the endoplasmic reticulum. J. Biol. Chem. 270, 2695-2702
8. Essalmani, R., Zaid, A., Marcinkiewicz, J., Chamberland, A., Pasquato, A., Seidah, N. G., and Prat, A. (2008) In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate. Proc. Natl. Acad. Sci. U.S.A. 105, 5750-5755 (Pubitemid 351758444)
9. Nakayama, K. (1997) Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins. Biochem. J. 327, 625-635
10. Seidah, N. G., Day, R., Marcinkiewicz, M., and Chrétien, M. (1998) Precursor convertases: an evolutionary ancient, cell-specific, combinatorial mechanism yielding diverse bioactive peptides and proteins. Ann. N.Y. Acad. Sci. 839, 9-24 (Pubitemid 28301755)
11. Portela-Gomes, G. M., Grimelius, L., and Stridsberg, M. (2008) Prohormone convertases 1/3, 2, furin and protein 7B2 (Secretogranin V) in endocrine cells of the human pancreas. Regul. Pept. 146, 117-124
12. Schäfer, M. K., Day, R., Cullinan, W. E., Chrétien, M., Seidah, N. G., and Watson, S. J. (1993) Gene expression of prohormone and proprotein convertases in the rat CNS: a comparative in situ hybridization analysis. J. Neurosci. 13, 1258-1279 (Pubitemid 23067609)
13. Day, R., Schafer, M. K., Watson, S. J., Chrétien, M., and Seidah, N. G. (1992) Distribution and regulation of the prohormone convertases PC1 and PC2 in the rat pituitary. Mol. Endocrinol. 6, 485-497
14. LaMendola, J., Martin, S. K., and Steiner, D. F. (1997) Expression of PC3, carboxypeptidase E and enkephalin in human monocyte-derived macrophages as a tool for genetic studies. FEBS Lett. 404, 19-22 (Pubitemid 27107799)
15. Vindrola, O., Mayer, A. M., Citera, G., Spitzer, J. A., and Espinoza, L. R. (1994) Prohormone convertases PC2 and PC3 in rat neutrophils and macrophages. Parallel changes with proenkephalin-derived peptides induced by LPS in vivo. Neuropeptides 27, 235-244 (Pubitemid 24329833)
16. Lansac, G., Dong, W., Dubois, C. M., Benlarbi, N., Afonso, C., Fournier, I., Salzet, M., and Day, R. (2006) Lipopolysaccharide mediated regulation of neuroendocrine associated proprotein convertases and neuropeptide precursor processing in the rat spleen. J. Neuroimmunol. 171, 57-71 (Pubitemid 41832278)
17. Salzet, M., Vieau, D., and Day, R. (2000) Crosstalk between nervous and immune systems through the animal kingdom: focus on opioids. Trends Neurosci. 23, 550-555
18. Salzet, M. (2001) Neuroimmunology of opioids from invertebrates to human. Neuro Endocrinol. Lett. 22, 467-474
19. Day, R., and Salzet, M. (2002) The neuroendocrine phenotype, cellular plasticity, and the search for genetic switches: redefining the diffuse neuroendocrine system. Neuro Endocrinol. Lett. 23, 447-451 (Pubitemid 36050024)
20. Akira, S., Takeda, K., and Kaisho, T. (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2, 675-680 (Pubitemid 32747155)
21. Lu, Y. C., Yeh, W. C., and Ohashi, P. S. (2008) LPS/TLR4 signal transduction pathway. Cytokine 42, 145-151
22. Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J., and Gusovsky, F. (1999) Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J. Biol. Chem. 274, 10689-10692
23. Rautajoki, K. J., Kylaniemi, M. K., Raghav, S. K., Rao, K., and Lahesmaa, R. (2008) An insight into molecular mechanisms of human T helper cell differentiation. Ann. Med. 40, 322-335 (Pubitemid 351882897)
24. Cottrez, F., Hurst, S. D., Coffman, R. L., and Groux, H. (2000) T regulatory cells 1 inhibit a Th2-specific response in vivo. J. Immunol. 165, 4848-4853
25. Schroder, K., Sweet, M. J., and Hume, D. A. (2006) Signal integration between IFNγ and TLR signalling pathways in macrophages. Immunobiology 211, 511-524
26. Puddu, P., Fantuzzi, L., Borghi, P., Varano, B., Rainaldi, G., Guillemard, E., Malorni, W., Nicaise, P., Wolf, S. F., Belardelli, F., and Gessani, S. (1997) IL-12 induces IFN-γ expression and secretion in mouse peritoneal macrophages. J. Immunol. 159, 3490-3497 (Pubitemid 127482108)
27. Fiorentino, D. F., Zlotnik, A., Mosmann, T. R., Howard, M., and O'Garra, A. (1991) IL-10 inhibits cytokine production by activated macrophages. J. Immunol. 147, 3815-3822
28. Kohyama, M., Ise, W., Edelson, B. T., Wilker, P. R., Hildner, K., Mejia, C., Frazier, W. A., Murphy, T. L., and Murphy, K. M. (2009) Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis. Nature 457, 318-321
29. Miyake, K. (2003) Innate recognition of lipopolysaccharide by CD14 and toll-like receptor 4-MD-2: unique roles for MD-2. Int. Immunopharmacol. 3, 119-128
30. Zhu, X., Zhou, A., Dey, A., Norrbom, C., Carroll, R., Zhang, C., Laurent, V., Lindberg, I., Ugleholdt, R., Holst, J. J., and Steiner, D. F. (2002) Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects. Proc. Natl. Acad. Sci. U.S.A. 99, 10293-10298
31. Dey, A., Xhu, X., Carroll, R., Turck, C. W., Stein, J., and Steiner, D. F. (2003) Biological processing of the cocaine and amphetamine-regulated transcript precursors by prohormone convertases, PC2 and PC1/3. J. Biol. Chem. 278, 15007-15014 (Pubitemid 36799833)
32. Marzban, L., Trigo-Gonzalez, G., Zhu, X., Rhodes, C. J., Halban, P. A., Steiner, D. F., and Verchere, C. B. (2004) Role of β-cell prohormone convertase (PC)1/3 in processing of pro-islet amyloid polypeptide. Diabetes 53, 141-148 (Pubitemid 38044708)
33. Ugleholdt, R., Poulsen, M. L., Holst, P. J., Irminger, J. C., Orskov, C., Pedersen, J., Rosenkilde, M. M., Zhu, X., Steiner, D. F., and Holst, J. J. (2006) Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor. J. Biol. Chem. 281, 11050-11057 (Pubitemid 43855528)
34. Wardman, J. H., Zhang, X., Gagnon, S., Castro, L. M., Zhu, X., Steiner, D. F., Day, R., and Fricker, L. D. (2010) Analysis of peptides in prohormone convertase 1/3 null mouse brain using quantitative peptidomics. J. Neurochem. 114, 215-225
35. Furuta, M., Yano, H., Zhou, A., Rouillé, Y., Holst, J. J., Carroll, R., Ravazzola, M., Orci, L., Furuta, H., and Steiner, D. F. (1997) Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2. Proc. Natl. Acad. Sci. U.S.A. 94, 6646-6651 (Pubitemid 27281918)
36. Villeneuve, P., Feliciangeli, S., Croissandeau, G., Seidah, N. G., Mbikay, M., Kitabgi, P., and Beaudet, A. (2002) Altered processing of the neurotensin/neuromedin N precursor in PC2 knock down mice: a biochemical and immunohistochemical study. J. Neurochem. 82, 783-793
37. D'Anjou, F., Routhier, S., Perreault, J. P., Latil, A., Bonnel, D., Fournier, I., Salzet, M., and Day, R. (2011) Molecular validation of PACE4 as a target in prostate cancer. Transl. Oncol. 4, 157-172
38. Wardman, J. H., Berezniuk, I., Di, S., Tasker, J. G., and Fricker, L. D. (2011) ProSAAS-derived peptides are colocalized with neuropeptide Y and function as neuropeptides in the regulation of food intake. PLoS One 6, e28152
39. Grenier, C., Bissonnette, C., Volkov, L., and Roucou, X. (2006) Molecular morphology and toxicity of cytoplasmic prion protein aggregates in neuronal and non-neuronal cells. J. Neurochem. 97, 1456-1466 (Pubitemid 43725584)
40. Benjannet, S., Rondeau, N., Paquet, L., Boudreault, A., Lazure, C., Chrétien, M., and Seidah, N. G. (1993) Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 and PC2. Biochem. J. 294, 735-743 (Pubitemid 23286561)
41. Polati, R., Castagna, A., Bossi, A., Campostrini, N., Zaninotto, F., Timperio, A. M., Zolla, L., Olivieri, O., Corrocher, R., and Girelli, D. (2009) High resolution preparation of monocyte-derived macrophages (MDM) protein fractions for clinical proteomics. Proteome Sci. 7, 4
42. Havlis, J., Thomas, H., Sebela, M., and Shevchenko, A. (2003) Fast-response proteomics by accelerated in-gel digestion of proteins. Anal. Chem. 75, 1300-1306 (Pubitemid 36397161)
43. Cesta, M. F. (2006) Normal structure, function, and histology of the spleen. Toxicol. Pathol. 34, 455-465
44. You, Y., Myers, R. C., Freeberg, L., Foote, J., Kearney, J. F., Justement, L. B., and Carter, R. H. (2011) Marginal zone B cells regulate antigen capture by marginal zone macrophages. J. Immunol. 186, 2172-2181
45. Jia, T., and Pamer, E. G. (2009) Immunology. Dispensable but not irrelevant. Science 325, 549-550
46. Takahashi, K., Shibata, T., Akashi-Takamura, S., Kiyokawa, T., Wakabayashi, Y., Tanimura, N., Kobayashi, T., Matsumoto, F., Fukui, R., Kouro, T., Nagai, Y., Takatsu, K., Saitoh, S., and Miyake, K. (2007) A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses. J. Exp. Med. 204, 2963-2976 (Pubitemid 350179564)
47. MacMicking, J. D., Nathan, C., Hom, G., Chartrain, N., Fletcher, D. S., Trumbauer, M., Stevens, K., Xie, Q. W., Sokol, K., Hutchinson, N., Chen, H., and Mudget, J. S. (1995) Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81, 641-650
48. Sriskandan, S., and Altmann, D. M. (2008) The immunology of sepsis. J. Pathol. 214, 211-223 (Pubitemid 351160158)
49. Keller, A., Nesvizhskii, A. I., Kolker, E., and Aebersold, R. (2002) Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal. Chem. 74, 5383-5392 (Pubitemid 35215372)
50. Nesvizhskii, A. I., Keller, A., Kolker, E., and Aebersold, R. (2003) A statistical model for identifying proteins by tandem mass spectrometry. Anal. Chem. 75, 4646-4658 (Pubitemid 37082259)
51. Nacife, V. P., Soeiro Mde, N., Gomes, R. N., D'Avila, H., Castro-Faria Neto, H. C., and Meirelles Mde, N. (2004) Morphological and biochemical characterization of macrophages activated by carrageenan and lipopolysaccharide in vivo. Cell Struct. Funct. 29, 27-34 (Pubitemid 39206717)
52. Moser, M., and Murphy, K. M. (2000) Dendritic cell regulation of TH1-TH2 development. Nat. Immunol. 1, 199-205
53. Mebius, R. E., and Kraal, G. (2005) Structure and function of the spleen. Nat. Rev. Immunol. 5, 606-616 (Pubitemid 41113192)
54. Roebroek, A. J., Umans, L., Pauli, I. G., Robertson, E. J., van Leuven, F., Van de Ven, W. J., and Constam, D. B. (1998) Failure of ventral closure and axial rotation in embryos lacking the proprotein convertase furin. Development 125, 4863-4876 (Pubitemid 29026768)
55. Mbikay, M., Tadros, H., Ishida, N., Lerner, C. P., De Lamirande, E., Chen, A., El-Alfy, M., Clermont, Y., Seidah, N. G., Chrétien, M., Gagnon, C., and Simpson, E. M. (1997) Impaired fertility in mice deficient for the testicular germ-cell protease PC4. Proc. Natl. Acad. Sci. U.S.A. 94, 6842-6846 (Pubitemid 27281952)
56. Constam, D. B., and Robertson, E. J. (2000) SPC4/PACE4 regulates a TGFβ signaling network during axis formation. Genes Dev. 14, 1146-1155 (Pubitemid 30324427)
57. Essalmani, R., Hamelin, J., Marcinkiewicz, J., Chamberland, A., Mbikay, M., Chrétien, M., Seidah, N. G., and Prat, A. (2006) Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouse. Mol. Cell. Biol. 26, 354-361
58. Yang, J., Goldstein, J. L., Hammer, R. E., Moon, Y. A., Brown, M. S., and Horton, J. D. (2001) Decreased lipid synthesis in livers of mice with disrupted Site-1 protease gene. Proc. Natl. Acad. Sci. U.S.A. 98, 13607-13612 (Pubitemid 33115945)
59. Abifadel, M., Varret, M., Rabès, J. P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., Derré, A., Villéger, L., Farnier, M., Beucler, I., Bruckert, E., Chambaz, J., Chanu, B., Lecerf, J. M., Luc, G., Moulin, P., Weissenbach, J., Prat, A., Krempf, M., Junien, C., Seidah, N. G., and Boileau, C. (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34, 154-156 (Pubitemid 36666925)
60. O'Rahilly, S., Gray, H., Humphreys, P. J., Krook, A., Polonsky, K. S., White, A., Gibson, S., Taylor, K., and Carr, C. (1995) Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N. Engl. J. Med. 333, 1386-1390
61. Jackson, R. S., Creemers, J. W., Ohagi, S., Raffin-Sanson, M. L., Sanders, L., Montague, C. T., Hutton, J. C., and O'Rahilly, S. (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat. Genet. 16, 303-306 (Pubitemid 27280217)
62. Jackson, R. S., Creemers, J. W., Farooqi, I. S., Raffin-Sanson, M. L., Varro, A., Dockray, G. J., Holst, J. J., Brubaker, P. L., Corvol, P., Polonsky, K. S., Ostrega, D., Becker, K. L., Bertagna, X., Hutton, J. C., White, A., Dattani, M. T., Hussain, K., Middleton, S. J., Nicole, T. M., Milla, P. J., Lindley, K. J., and O'Rahilly, S. (2003) Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J. Clin. Investig. 112, 1550-1560 (Pubitemid 38056281)
63. Farooqi, I. S., Volders, K., Stanhope, R., Heuschkel, R., White, A., Lank, E., Keogh, J., O'Rahilly, S., and Creemers, J. W. (2007) Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J. Clin. Endocrinol. Metab. 92, 3369-3373 (Pubitemid 47435306)
64. Ugleholdt, R., Zhu, X., Deacon, C. F., Ørskov, C., Steiner, D. F., and Holst, J. J. (2004) Impaired intestinal proglucagon processing in mice lacking prohormone convertase 1. Endocrinology 145, 1349-1355 (Pubitemid 38281019)
65. Furuta, M., Zhou, A., Webb, G., Carroll, R., Ravazzola, M., Orci, L., and Steiner, D. F. (2001) Severe defect in proglucagon processing in islet A-cells of prohormone convertase 2 null mice. J. Biol. Chem. 276, 27197-27202
66. Pan, H., Che, F. Y., Peng, B., Steiner, D. F., Pintar, J. E., and Fricker, L. D. (2006) The role of prohormone convertase-2 in hypothalamic neuropeptide processing: a quantitative neuropeptidomic study. J. Neurochem. 98, 1763-1777 (Pubitemid 44298243)
67. Pasparakis, M., Alexopoulou, L., Episkopou, V., and Kollias, G. (1996) Immune and inflammatory responses in TNFα-deficient mice: a critical requirement for TNFα in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J. Exp. Med. 184, 1397-1411 (Pubitemid 26354696)
68. Tumanov, A. V., Grivennikov, S. I., Shakhov, A. N., Rybtsov, S. A., Koroleva, E. P., Takeda, J., Nedospasov, S. A., and Kuprash, D. V. (2003) Dissecting the role of lymphotoxin in lymphoid organs by conditional targeting. Immunol. Rev. 195, 106-116 (Pubitemid 37153457)
69. Rittirsch, D., Flierl, M. A., and Ward, P. A. (2008) Harmful molecular mechanisms in sepsis. Nat. Rev. Immunol. 8, 776-787
70. Zanoni, I., and Granucci, F. (2009) Dendritic cells and macrophages: same receptors but different functions. Curr. Immunol. Rev. 5, 311-325
71. Kamath, A. T., Pooley, J., O'Keeffe, M. A., Vremec, D., Zhan, Y., Lew, A. M., D'Amico, A., Wu, L., Tough, D. F., and Shortman, K. (2000) The development, maturation, and turnover rate of mouse spleen dendritic cell populations. J. Immunol. 165, 6762-6770 (Pubitemid 32001141)
72. Rittig, M. G., Wilske, B., and Krause, A. (1999) Phagocytosis of microorganisms by means of overshooting pseudopods: where do we stand? Microbes Infect. 1, 727-735
73. Isaac, B. M., Ishihara, D., Nusblat, L. M., Gevrey, J. C., Dovas, A., Condeelis, J., and Cox, D. (2010) N-WASP has the ability to compensate for the loss of WASP in macrophage podosome formation and chemotaxis. Exp. Cell Res. 316, 3406-3416
74. Blott, E. J., and Griffiths, G. M. (2002) Secretory lysosomes. Nat. Rev. Mol. Cell Biol. 3, 122-131
75. Duitman, E. H., Orinska, Z., and Bulfone-Paus, S. (2011) Mechanisms of cytokine secretion: a portfolio of distinct pathways allows flexibility in cytokine activity. Eur. J. Cell Biol. 90, 476-483
76. Stow, J. L., Low, P. C., Offenhäuser, C., and Sangermani, D. (2009) Cytokine secretion in macrophages and other cells: pathways and mediators. Immunobiology 214, 601-612
77. Dikeakos, J. D., Di Lello, P., Lacombe, M. J., Ghirlando, R., Legault, P., Reudelhuber, T. L., and Omichinski, J. G. (2009) Functional and structural characterization of a dense core secretory granule sorting domain from the PC1/3 protease. Proc. Natl. Acad. Sci. U.S.A. 106, 7408-7413
78. Dikeakos, J. D., and Reudelhuber, T. L. (2007) Sending proteins to dense core secretory granules: still a lot to sort out. J. Cell Biol. 177, 191-196 (Pubitemid 46658630)
79. Saint-Pol, A., Yélamos, B., Amessou, M., Mills, I. G., Dugast, M., Tenza, D., Schu, P., Antony, C., McMahon, H. T., Lamaze, C., and Johannes, L. (2004) Clathrin adaptor epsinR is required for retrograde sorting on early endosomal membranes. Dev. Cell 6, 525-538 (Pubitemid 38456181)
80. Jean, F., Basak, A., Rondeau, N., Benjannet, S., Hendy, G. N., Seidah, N. G., Chrétien, M., and Lazure, C. (1993) Enzymic characterization of murine and human prohormone convertase-1 (mPC1 and hPC1) expressed in mammalian GH4C1 cells. Biochem. J. 292, 891-900 (Pubitemid 23210226)
81. Haddad, J. J., Saadé, N. E., and Safieh-Garabedian, B. (2002) Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary- adrenal revolving axis. J. Neuroimmunol. 133, 1-19 (Pubitemid 35346723)
82. Sternberg, E. M. (2006) Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nat. Rev. Immunol. 6, 318-328
83. Straub, R. H., Schaller, T., Miller, L. E., von Hörsten, S., Jessop, D. S., Falk, W., and Schölmerich, J. (2000) Neuropeptide Y cotransmission with norepinephrine in the sympathetic nerve-macrophage interplay. J. Neurochem. 75, 2464-2471
84. Cope, A., Le Friec, G., Cardone, J., and Kemper, C. (2011) The Th1 life cycle: molecular control of IFN-γ to IL-10 switching. Trends Immunol. 32, 278-286
85. + T cells through IL-12 produced by Listeria-induced macrophages. Science 260, 547-549
86. Anderson, C. F., and Mosser, D. M. (2002) Cutting edge: biasing immune responses by directing antigen to macrophage Fcγ receptors. J. Immunol. 168, 3697-3701 (Pubitemid 34298366)
87. Mantovani, A., Sica, A., Sozzani, S., Allavena, P., Vecchi, A., and Locati, M. (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 25, 677-686 (Pubitemid 39457982)
88. Gordon, S. (2003) Alternative activation of macrophages. Nat. Rev. Immunol. 3, 23-35
89. Murray, H. W., Spitalny, G. L., and Nathan, C. F. (1985) Activation of mouse peritoneal macrophages in vitro and in vivo by interferon-γ. J. Immunol. 134, 1619-1622 (Pubitemid 15130280)
90. Schroder, K., Hertzog, P. J., Ravasi, T., and Hume, D. A. (2004) Interferon- γ: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 75, 163-189 (Pubitemid 38174573)
91. Taams, L. S., van Amelsfort, J. M., Tiemessen, M. M., Jacobs, K. M., de Jong, E. C., Akbar, A. N., Bijlsma, J. W., and Lafeber, F. P. (2005) Modulation of monocyte/macrophage function by human CD4+CD25+ regulatory T cells. Hum. Immunol. 66, 222-230 (Pubitemid 40395242)
92. Harding, C. V. (1995) Phagocytic processing of antigens for presentation by MHC molecules. Trends Cell Biol. 5, 105-109
93. Blander, J. M., and Medzhitov, R. (2004) Regulation of phagosome maturation by signals from toll-like receptors. Science 304, 1014-1018 (Pubitemid 38638100)
94. Wang, Y., Chen, T., Han, C., He, D., Liu, H., An, H., Cai, Z., and Cao, X. (2007) Lysosome-associated small Rab GTPase Rab7b negatively regulates TLR4 signaling in macrophages by promoting lysosomal degradation of TLR4. Blood 110, 962-971 (Pubitemid 47267435)
95. Wang, Y. C., He, F., Feng, F., Liu, X. W., Dong, G. Y., Qin, H. Y., Hu, X. B., Zheng, M. H., Liang, L., Feng, L., Liang, Y. M., and Han, H. (2010) Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses. Cancer Res. 70, 4840-4849
96. Kim, R., Emi, M., and Tanabe, K. (2005) Cancer cell immune escape and tumor progression by exploitation of anti-inflammatory and pro-inflammatory responses. Cancer Biol. Ther. 4, 924-933 (Pubitemid 41598585)
97. Baecher-Allan, C., and Hafler, D. A. (2006) Human regulatory T cells and their role in autoimmune disease. Immunol. Rev. 212, 203-216 (Pubitemid 44116710)
98. Gereda, J. E., Leung, D. Y., Thatayatikom, A., Streib, J. E., Price, M. R., Klinnert, M. D., and Liu, A. H. (2000) Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet 355, 1680-1683 (Pubitemid 30248480)