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Heparanase is Involved in Leukocyte Migration

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Heparanase

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1221))

Abstract

Leukocyte migration is essential for exerting self-defense mechanisms. During the extravasation process, leukocytes transmigrate through the endothelial lining and the subendothelial basement membrane. Accumulating evidence supports the involvement of heparanase in this process. Altered cellular distribution resulting in relocalization of heparanase to the leading edge of migration is a key event to rapidly turn on the function of the enzyme during migration. This review presents current research investigating the cellular machinery that builds up a functional subcellular structure for leukocyte attachment to and degradation of the extracellular matrix. Recent advances in the understanding of the roles of heparanase in inflammatory diseases and pharmacological approaches to control heparanase-mediated actions during inflammation are also discussed.

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Abbreviations

BM:

Basement Membrane

CAR:

Chimeric Antigen Receptor

fMLP:

formyl Methionyl Leucyl Phenylalanine

Hpse:

Heparanase

HSPG:

Heparan Sulfate Proteoglycan

MMP:

Matrix Metalloproteinase

References

  1. Baruzzi, A., Remelli, S., Lorenzetto, E., Sega, M., Chignola, R., & Berton, G. (2015). Sos1 regulates macrophage podosome assembly and macrophage invasive capacity. The Journal of Immunology, 195(10), 4900–4912.

    Google Scholar 

  2. Benhamron, S., Nechushtan, H., Verbovetski, I., Krispin, A., Abboud-Jarrous, G., Zcharia, E., Edovitsky, E., Nahari, E., Peretz, T., Vlodavsky, I., & Mevorach, D. (2006). Translocation of active heparanase to cell surface regulates degradation of extracellular matrix heparan sulfate upon transmigration of mature monocyte-derived dendritic cells. The Journal of Immunology, 176(11), 6417–6424.

    Google Scholar 

  3. Benhamron, S., Reiner, I., Zcharia, E., Atallah, M., Grau, A., Vlodavsky, I., & Mevorach, D. (2012). Dissociation between mature phenotype and impaired transmigration in dendritic cells from heparanase-deficient mice. PLoS One, 7(5), e35602.

    Article  CAS  Google Scholar 

  4. Caruana, I., Savoldo, B., Hoyos, V., Weber, G., Liu, H., Kim, E. S., Ittmann, M. M., Marchetti, D., & Dotti, G. (2015). Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nature Medicine, 21(5), 524–529.

    Article  CAS  Google Scholar 

  5. Edovitsky, E., Lerner, I., Zcharia, E., Peretz, T., Vlodavsky, I., & Elkin, M. (2006). Role of endothelial heparanase in delayed-type hypersensitivity. Blood, 107(9), 3609–3616.

    Article  CAS  Google Scholar 

  6. Jevnikar, Z., Mirković, B., Fonović, U. P., Zidar, N., Švajger, U., & Kos, J. (2012). Three-dimensional invasion of macrophages is mediated by cysteine cathepsins in protrusive podosomes. European Journal of Immunology, 42(12), 3429–3441.

    Article  CAS  Google Scholar 

  7. Komatsu, N., Waki, M., Sue, M., Tokuda, C., Kasaoka, T., Nakajima, M., Higashi, N., & Irimura, T. (2008). Heparanase expression in B16 melanoma cells and peripheral blood neutrophils before and after extravasation detected by novel anti-mouse heparanase monoclonal antibodies. Journal of Immunological Methods, 331, 82–93.

    Article  CAS  Google Scholar 

  8. Ley, K., Laudanna, C., Cybulsky, M. I., & Nourshargh, S. (2007). Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nature Reviews Immunology, 7(9), 678–689.

    Article  CAS  Google Scholar 

  9. Massena, S., Christoffersson, G., Hjertström, E., Zcharia, E., Vlodavsky, I., Ausmees, N., Rolny, C., Li, J. P., & Phillipson, M. (2010). A chemotactic gradient sequestered on endothelial heparan sulfate induces directional intraluminal crawling of neutrophils. Blood, 116(11), 1924–1931.

    Article  CAS  Google Scholar 

  10. Moldovan, N. I., Goldschmidt-Clermont, P. J., Parker-Thornburg, J., Shapiro, S. D., & Kolattukudy, P. E. (2000). Contribution of monocytes/macrophages to compensatory neovascularization: the drilling of metalloelastase-positive tunnels in ischemic myocardium. Circulation Research, 87(5), 378–384.

    Article  CAS  Google Scholar 

  11. Mollinedo, F., Nakajima, M., Llorens, A., Barbosa, E., Callejo, S., Gajate, C., & Fabra, A. (1997). Major co-localization of the extracellular-matrix degradative enzymes heparanase and gelatinase in tertiary granules of human neutrophils. Biochemical Journal, 327(3), 917–923.

    Google Scholar 

  12. Morris, A., Wang, B., Waern, I., Venkatasamy, R., Page, C., Schmidt, E. P., Wernersson, S., Li, J. P., & Spina, D. (2015). The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus. PLoS One, 10(6), e0127032.

    Article  Google Scholar 

  13. Nakajima, M., Irimura, T., Di Ferrante, D., Di Ferrante, N., & Nicolson, G. L. (1983). Heparan sulfate degradation: relation to tumor invasive and metastatic properties of mouse B16 melanoma sublines. Science, 220(4597), 611–613.

    Google Scholar 

  14. Nishimura, Y., Shitara, E., Adachi, H., Toyoshima, M., Nakajima, M., Okami, Y., & Takeuchi, T. (2000). Flexible synthesis and biological activity of uronic acid-type gem-diamine 1-N-iminosugars: a new family of glycosidase inhibitors. The Journal of Organic Chemistry, 65(1), 2–11.

    Article  CAS  Google Scholar 

  15. Poon, I. K., Goodall, K. J., Phipps, S., Chow, J. D., Pagler, E. B., Andrews, D. M., Conlan, C. L., Ryan, G. F., White, J. A., Wong, M. K., Horan, C., Matthaei, K. I., Smyth, M. J., & Hulett, M. D. (2014). Mice deficient in heparanase exhibit impaired dendritic cell migration and reduced airway inflammation. European Journal of Immunology, 44(4), 1016–1030.

    Article  CAS  Google Scholar 

  16. Sasaki, N., Higashi, N., Taka, T., Nakajima, M., & Irimura, T. (2004). Cell surface localization of heparanase on macrophages regulates degradation of extracellular matrix heparan sulfate. The Journal of Immunology, 172(6), 3830–3835.

    Google Scholar 

  17. Schmidt, E. P., Yang, Y., Janssen, W. J., Gandjeva, A., Perez, M. J., Barthel, L., Zemans, R. L., Bowman, J. C., Koyanagi, D. E., Yunt, Z. X., Smith, L. P., Cheng, S. S., Overdier, K. H., Thompson, K. R., Geraci, M. W., Douglas, I. S., Pearse, D. B., & Tuder, R. M. (2012). The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nature Medicine, 18(8), 1217–1223.

    Article  CAS  Google Scholar 

  18. Stoler-Barak, L., Moussion, C., Shezen, E., Hatzav, M., Sixt, M., & Alon, R. (2014). Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects. PLoS One, 9(1), e85699.

    Article  Google Scholar 

  19. Stoler-Barak, L., Petrovich, E., Aychek, T., Gurevich, I., Tal, O., Hatzav, M., Ilan, N., Feigelson, S. W., Shakhar, G., Vlodavsky, I., & Alon, R. (2015). Heparanase of murine effector lymphocytes and neutrophils is not required for their diapedesis into sites of inflammation. The FASEB Journal, 29(5), 2010–2021.

    Article  CAS  Google Scholar 

  20. Su, A. I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K. A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., Cooke, M. P., Walker, J. R., & Hogenesch, J. B. (2005). A gene atlas of the mouse and human protein-encoding transcriptomes. Proceedings of the National Academy of Sciences of the United States of America, 101(16), 6062–6067.

    Article  Google Scholar 

  21. Sue, M., Higashi, N., Shida, H., Kogane, Y., Nishimura, Y., Adachi, H., Kolaczkowska, E., Kepka, M., Nakajima, M., & Irimura, T. (2016). An iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouches. International Immunopharmacology, 35, 15–21.

    Article  CAS  Google Scholar 

  22. Vlodavsky, I., Eldor, A., Haimovitz-Friedman, A., Matzner, Y., Ishai-Michaeli, R., Lider, O., Naparstek, Y., Cohen, I. R., & Fuks, Z. (1992). Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation. Invasion Metastasis, 12(2), 112–127.

    CAS  PubMed  Google Scholar 

  23. Voisin, M. B., Woodfin, A., & Nourshargh, S. (2009). Monocytes and neutrophils exhibit both distinct and common mechanisms in penetrating the vascular basement membrane in vivo. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(8), 1193–1199.

    Article  CAS  Google Scholar 

  24. Wang, S., Voisin, M. B., Larbi, K. Y., Dangerfield, J., Scheiermann, C., Tran, M., Maxwell, P. H., Sorokin, L., & Nourshargh, S. (2006). Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. The Journal of Experimental Medicine, 203(6), 1519–1532.

    Article  CAS  Google Scholar 

  25. Wiesner, C., Le-Cabec, V., El Azzouzi, K., Maridonneau-Parini, I., & Linder, S. (2014). Podosomes in space: macrophage migration and matrix degradation in 2D and 3D settings. Cell Adhesion & Migration, 8(3), 179–191.

    Google Scholar 

  26. Ziolkowski, A. F., Popp, S. K., Freeman, C., Parish, C. R., & Simeonovic, C. J. (2012). Heparan sulfate and heparanase play key roles in mouse β cell survival and autoimmune diabetes. The Journal of Clinical Investigation, 122, 132–141.

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Biochemistry, Hoshi University School of Pharmacy, Tokyo, Japan

    Nobuaki Higashi

  2. Division of Glycobiologics, Intractable Disease Research Center, Juntendo University School of Medicine, Tokyo, Japan

    Tatsuro Irimura

  3. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan

    Tatsuro Irimura

  4. SBI Pharmaceuticals Co., Ltd, Minato-ku, Tokyo, Japan

    Motowo Nakajima

Authors
  1. Nobuaki Higashi
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  2. Tatsuro Irimura
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  3. Motowo Nakajima
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Corresponding author

Correspondence to Nobuaki Higashi .

Editor information

Editors and Affiliations

  1. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Israel Vlodavsky

  2. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

    Ralph D. Sanderson

  3. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Neta Ilan

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Higashi, N., Irimura, T., Nakajima, M. (2020). Heparanase is Involved in Leukocyte Migration. In: Vlodavsky, I., Sanderson, R., Ilan, N. (eds) Heparanase. Advances in Experimental Medicine and Biology, vol 1221. Springer, Cham. https://doi.org/10.1007/978-3-030-34521-1_16

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