Journal of Yeungnam Medical Science

Yeungnam University College of Medicine, Yeungnam University Institute Medical Science (영남대 의대 학술지 편집위원회)
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Sulfatase 1 and sulfatase 2 as novel regulators of macrophage antigen presentation and phagocytosis

  • Kim, Hyun-Je (Division of Rheumatology, Department of Internal Medicine, CHA University, CHA Gumi Medical Center) ;
  • Kim, Hee-Sun (Department of Microbiology, Yeungnam University College of Medicine) ;
  • Hong, Young-Hoon (Division of Rheumatology, Department of Internal Medicine, Yeungnam University College of Medicine)
  • Received : 2021.03.23
  • Accepted : 2021.05.25
  • Published : 2021.10.31
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Abstract

Background: Sulfation of heparan sulfate proteoglycans (HSPGs) is critical for the binding and signaling of ligands that mediate inflammation. Extracellular 6-O-endosulfatases regulate posttranslational sulfation levels and patterns of HSPGs. In this study, extracellular 6-O-endosulfatases, sulfatase (Sulf)-1 and Sulf-2, were evaluated for their expression and function in inflammatory cells and tissues. Methods: Harvested human peripheral blood mononuclear cells were treated with phytohemagglutinin and lipopolysaccharide, and murine peritoneal macrophages were stimulated with interleukin (IL)-1β for the evaluation of Sulf-1 and Sulf-2 expression. Sulf expression in inflammatory cells was examined in the human rheumatoid arthritis (RA) synovium by immunofluorescence staining. The antigen presentation and phagocytic activities of macrophages were compared according to the expression state of Sulfs. Sulfs-knockdown macrophages and Sulfs-overexpressing macrophages were generated using small interfering RNAs and pcDNA3.1 plasmids for Sulf-1 and Sulf-2, respectively. Results: Lymphocytes and monocytes showed weak Sulf expression, which remained unaffected by IL-1β. However, peritoneal macrophages showed increased expression of Sulfs upon stimulation with IL-1β. In human RA synovium, two-colored double immunofluorescent staining of Sulfs and CD68 revealed active upregulation of Sulfs in macrophages of inflamed tissues, but not in lymphocytes of lymphoid follicles. Macrophages are professional antigen-presenting cells. The antigen presentation and phagocytic activities of macrophages were dependent on the level of Sulf expression, suppressed in Sulfs-knockdown macrophages, and enhanced in Sulfs-overexpressing macrophages. Conclusion: The results demonstrate that upregulation of Sulfs in macrophages occurs in response to inflammation, and Sulfs actively regulate the antigen presentation and phagocytic activities of macrophages as novel immune regulators.

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References

  1. Dreyfuss JL, Regatieri CV, Jarrouge TR, Cavalheiro RP, Sampaio LO, Nader HB. Heparan sulfate proteoglycans: structure, protein interactions and cell signaling. An Acad Bras Cienc 2009;81:409-29. https://doi.org/10.1590/S0001-37652009000300007
  2. Clasper S, Vekemans S, Fiore M, Plebanski M, Wordsworth P, David G, et al. Inducible expression of the cell surface heparan sulfate proteoglycan syndecan-2 (fibroglycan) on human activated macrophages can regulate fibroblast growth factor action. J Biol Chem 1999;274:24113-23. https://doi.org/10.1074/jbc.274.34.24113
  3. Parish CR. The role of heparan sulphate in inflammation. Nat Rev Immunol 2006;6:633-43. https://doi.org/10.1038/nri1918
  4. Vanpouille C, Deligny A, Delehedde M, Denys A, Melchior A, Lienard X, et al. The heparin/heparan sulfate sequence that interacts with cyclophilin B contains a 3-O-sulfated N-unsubstituted glucosamine residue. J Biol Chem 2007;282:24416-29. https://doi.org/10.1074/jbc.M701835200
  5. Matsuo I, Kimura-Yoshida C. Extracellular modulation of fibroblast growth factor signaling through heparan sulfate proteoglycans in mammalian development. Curr Opin Genet Dev 2013;23:399-407. https://doi.org/10.1016/j.gde.2013.02.004
  6. Witt DP, Lander AD. Differential binding of chemokines to glycosaminoglycan subpopulations. Curr Biol 1994;4:394-400. https://doi.org/10.1016/s0960-9822(00)00088-9
  7. Wang L, Fuster M, Sriramarao P, Esko JD. Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses. Nat Immunol 2005;6:902-10. https://doi.org/10.1038/ni1233
  8. Rops AL, van den Hoven MJ, Baselmans MM, Lensen JF, Wijnhoven TJ, van den Heuvel LP, et al. Heparan sulfate domains on cultured activated glomerular endothelial cells mediate leukocyte trafficking. Kidney Int 2008;73:52-62. https://doi.org/10.1038/sj.ki.5002573
  9. Kawashima H. Roles of sulfated glycans in lymphocyte homing. Biol Pharm Bull 2006;29:2343-9. https://doi.org/10.1248/bpb.29.2343
  10. van der Voort R, Keehnen RM, Beuling EA, Spaargaren M, Pals ST. Regulation of cytokine signaling by B cell antigen receptor and CD40-controlled expression of heparan sulfate proteoglycans. J Exp Med 2000;192:1115-24. https://doi.org/10.1084/jem.192.8.1115
  11. Floris S, van den Born J, van der Pol SM, Dijkstra CD, De Vries HE. Heparan sulfate proteoglycans modulate monocyte migration across cerebral endothelium. J Neuropathol Exp Neurol 2003;62:780-90. https://doi.org/10.1093/jnen/62.7.780
  12. Celie JW, Rutjes NW, Keuning ED, Soininen R, Heljasvaara R, Pihlajaniemi T, et al. Subendothelial heparan sulfate proteoglycans become major L-selectin and monocyte chemoattractant protein-1 ligands upon renal ischemia/reperfusion. Am J Pathol 2007;170:1865-78. https://doi.org/10.2353/ajpath.2007.070061
  13. Diez-Roux G, Ballabio A. Sulfatases and human disease. Annu Rev Genomics Hum Genet 2005;6:355-79. https://doi.org/10.1146/annurev.genom.6.080604.162334
  14. Dhoot GK, Gustafsson MK, Ai X, Sun W, Standiford DM, Emerson CP Jr. Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase. Science 2001;293:1663-6. https://doi.org/10.1126/science.293.5535.1663
  15. Morimoto-Tomita M, Uchimura K, Werb Z, Hemmerich S, Rosen SD. Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans. J Biol Chem 2002;277:49175-85. https://doi.org/10.1074/jbc.M205131200
  16. Ohto T, Uchida H, Yamazaki H, Keino-Masu K, Matsui A, Masu M. Identification of a novel nonlysosomal sulphatase expressed in the floor plate, choroid plexus and cartilage. Genes Cells 2002;7:173-85. https://doi.org/10.1046/j.1356-9597.2001.00502.x
  17. Ai X, Do AT, Lozynska O, Kusche-Gullberg M, Lindahl U, Emerson CP Jr. QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling. J Cell Biol 2003;162:341-51. https://doi.org/10.1083/jcb.200212083
  18. Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, et al. Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem 1999;68:729-77. https://doi.org/10.1146/annurev.biochem.68.1.729
  19. Esko JD, Lindahl U. Molecular diversity of heparan sulfate. J Clin Invest 2001;108:169-73. https://doi.org/10.1172/JCI13530
  20. Jackson DG. Human leucocyte heparan sulphate proteoglycans and their roles in inflammation. Biochem Soc Trans 1997;25:220-4. https://doi.org/10.1042/bst0250220
  21. Camp RL, Scheynius A, Johansson C, Pure E. CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation. J Exp Med 1993;178:497-507. https://doi.org/10.1084/jem.178.2.497
  22. Mikecz K, Brennan FR, Kim JH, Glant TT. Anti-CD44 treatment abrogates tissue oedema and leukocyte infiltration in murine arthritis. Nat Med 1995;1:558-63. https://doi.org/10.1038/nm0695-558
  23. Kim JH, Chan C, Elwell C, Singer MS, Dierks T, Lemjabbar-Alaoui H, et al. Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection. Cell Microbiol 2013;15:1560-71. https://doi.org/10.1111/cmi.12133
  24. Habuchi H, Habuchi O, Kimata K. Sulfation pattern in glycosaminoglycan: does it have a code? Glycoconj J 2004;21:47-52. https://doi.org/10.1023/B:GLYC.0000043747.87325.5e
  25. Nawroth R, van Zante A, Cervantes S, McManus M, Hebrok M, Rosen SD. Extracellular sulfatases, elements of the Wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. PLoS One 2007;2:e392. https://doi.org/10.1371/journal.pone.0000392
  26. Lemjabbar-Alaoui H, van Zante A, Singer MS, Xue Q, Wang YQ, Tsay D, et al. Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis. Oncogene 2010;29:635-46. https://doi.org/10.1038/onc.2009.365
  27. Bret C, Moreaux J, Schved JF, Hose D, Klein B. SULFs in human neoplasia: implication as progression and prognosis factors. J Transl Med 2011;9:72. https://doi.org/10.1186/1479-5876-9-72
  28. Yang JD, Sun Z, Hu C, Lai J, Dove R, Nakamura I, et al. Sulfatase 1 and sulfatase 2 in hepatocellular carcinoma: associated signaling pathways, tumor phenotypes, and survival. Genes Chromosomes Cancer 2011;50:122-35. https://doi.org/10.1002/gcc.20838
  29. Nagamine S, Koike S, Keino-Masu K, Masu M. Expression of a heparan sulfate remodeling enzyme, heparan sulfate 6-O-endosulfatase sulfatase FP2, in the rat nervous system. Brain Res Dev Brain Res 2005;159:135-43. https://doi.org/10.1016/j.devbrainres.2005.07.006
  30. Buono M, Visigalli I, Bergamasco R, Biffi A, Cosma MP. Sulfatase modifying factor 1-mediated fibroblast growth factor signaling primes hematopoietic multilineage development. J Exp Med 2010;207:1647-60. https://doi.org/10.1084/jem.20091022
  31. Langsdorf A, Schumacher V, Shi X, Tran T, Zaia J, Jain S, et al. Expression regulation and function of heparan sulfate 6-O-endosulfatases in the spermatogonial stem cell niche. Glycobiology 2011;21:152-61. https://doi.org/10.1093/glycob/cwq133
  32. Otsuki S, Taniguchi N, Grogan SP, D'Lima D, Kinoshita M, Lotz M. Expression of novel extracellular sulfatases Sulf-1 and Sulf-2 in normal and osteoarthritic articular cartilage. Arthritis Res Ther 2008;10:R61. https://doi.org/10.1186/ar2432
  33. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 2011;11:723-37. https://doi.org/10.1038/nri3073
  34. Roche PA, Furuta K. The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol 2015;15:203-16. https://doi.org/10.1038/nri3818
  35. Guermonprez P, Valladeau J, Zitvogel L, Thery C, Amigorena S. Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 2002;20:621-67. https://doi.org/10.1146/annurev.immunol.20.100301.064828
  36. Leonetti M, Gadzinski A, Moine G. Cell surface heparan sulfate proteoglycans influence MHC class II-restricted antigen presentation. J Immunol 2010;185:3847-56. https://doi.org/10.4049/jimmunol.0902724
  37. Dehio C, Freissler E, Lanz C, Gomez-Duarte OG, David G, Meyer TF. Ligation of cell surface heparan sulfate proteoglycans by antibody-coated beads stimulates phagocytic uptake into epithelial cells: a model for cellular invasion by Neisseria gonorrhoeae. Exp Cell Res 1998;242:528-39. https://doi.org/10.1006/excr.1998.4116
  38. Reis CR, Chen PH, Srinivasan S, Aguet F, Mettlen M, Schmid SL. Crosstalk between Akt/GSK3β signaling and dynamin-1 regulates clathrin-mediated endocytosis. EMBO J 2015;34:2132-46. https://doi.org/10.15252/embj.201591518
  39. van Deurs B, Ropke C, Thorball N. Kinetics of pinocytosis studied by flow cytometry. Eur J Cell Biol 1984;34:96-102.
  40. Ishimoto H, Yanagihara K, Araki N, Mukae H, Sakamoto N, Izumikawa K, et al. Single-cell observation of phagocytosis by human blood dendritic cells. Jpn J Infect Dis 2008;61:294-7.