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Involvement of very long fatty acid-containing lactosylceramide in lactosylceramide-mediated superoxide generation and migration in neutrophils

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An Erratum to this article was published on 26 January 2008

Abstract

The neutral glycosphingolipid lactosylceramide (LacCer) forms lipid rafts (membrane microdomains) coupled with the Src family kinase Lyn on the plasma membranes of human neutrophils; ligand binding to LacCer activates Lyn, resulting in neutrophil functions, such as superoxide generation and migration (Iwabuchi and Nagaoka, Lactosylceramide-enriched glycosphingolipid signaling domain mediates superoxide generation from human neutrophils, Blood 100, 1454–1464, 2002 and Sato et al. Induction of human neutrophil chemotaxis by Candida albicans-derived beta-1,6-long glycoside side-chain-branched beta glycan, J. Leukoc. Biol. 84, 204–211, 2006). Neutrophilic differentiated HL-60 cells (D-HL-60 cells) express almost the same amount of LacCer as neutrophils. However, D-HL-60 cells do not have Lyn-associated LacCer-enriched lipid rafts and lack LacCer-mediated superoxide-generating and migrating abilities. Here, we examined the roles of LacCer molecular species of different fatty acid compositions in these processes. Liquid chromatography-mass spectrometry analyses revealed that the very long fatty acid C24:0 and C24:1 chains were the main components of LacCer (31.6% on the total fatty acid content) in the detergent-resistant membrane fraction (DRM) from neutrophil plasma membranes. In contrast, plasma membrane DRM of D-HL-60 cells included over 70% C16:0-LacCer, but only 13.6% C24-LacCer species. D-HL-60 cells loaded with C24:0 or C24:1-LacCer acquired LacCer-mediated migrating and superoxide-generating abilities, and allowed Lyn coimmunoprecipitation by anti-LacCer antibody. Lyn knockdown by siRNA completely abolished the effect of C24:1-LacCer loading on LacCer-mediated migration of D-HL-60 cells. Immunoelectron microscopy revealed that LacCer clusters were closely associated with Lyn molecules in neutrophils and C24:1-LacCer-loaded D-HL-60 cells, but not in D-HL-60 cells or C16:0-LacCer-loaded cells. Taken together, these observations suggest that LacCer species with very long fatty acids are specifically necessary for Lyn-coupled LacCer-enriched lipid raft-mediated neutrophil superoxide generation and migration.

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Abbreviations

DMSO:

Dimethyl sulfoxide

D-HL-60 cells:

DMSO-treated neutrophilic differentiated human promyelocytic leukemia HL-60 cells

fMLP:

Formyl peptide (N-formyl-methionyl-leucyl-phenylalanine)

CSBG:

Candida albicans-derived β-glucan

SCG:

Sparassis crispa-derived β-glucan

SM:

Sphingomyelin

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

References

  1. Degroote, S., Wolthoorn, J., van Meer, G.: The cell biology of glycosphingolipids. Semin. Cell. Dev. Biol. 15, 375–387 (2004)

    Article  PubMed  CAS  Google Scholar 

  2. Hakomori, S.: Structure, organization, and function of glycosphingolipids in membrane. Curr. Opin. Hematol. 10, 16–24 (2003)

    Article  PubMed  CAS  Google Scholar 

  3. Kaga, N., Kazuno, S., Taka, H., Iwabuchi, K., Murayama, K.: Isolation and mass spectrometry characterization of molecular species of lactosylceramides using liquid chromatography-electrospray ion trap mass spectrometry. Anal. Biochem. 337, 316–324 (2005)

    Article  PubMed  CAS  Google Scholar 

  4. Sonnino, S., Prinetti, A., Mauri, L., Chigorno, V., Tettamanti, G.: Dynamic and structural properties of sphingolipids as driving forces for the formation of membrane domains. Chem. Rev. 106, 2111–2125 (2006)

    Article  PubMed  CAS  Google Scholar 

  5. Brackman, D., Lund-Johansen, F., Aarskog, D.: Expression of leukocyte differentiation antigens during the differentiation of HL-60 cells induced by 1,25-dihydroxyvitamin D3: comparison with the maturation of normal monocytic and granulocytic bone marrow cells. J. Leukoc. Biol. 58, 547–555 (1995)

    PubMed  CAS  Google Scholar 

  6. Brown, D.A., London, E.: Structure of detergent-resistant membrane domains: does phase separation occur in biological membranes? Biochem. Biophys. Res. Commun. 240, 1–7 (1997)

    Article  PubMed  CAS  Google Scholar 

  7. Iwabuchi, K., Handa, K., Hakomori, S.: Separation of “glycosphingolipid signaling domain” from caveolin-containing membrane fraction in mouse melanoma B16 cells and its role in cell adhesion coupled with signaling. J. Biol. Chem. 273, 33766–33773 (1998)

    Article  PubMed  CAS  Google Scholar 

  8. Iwabuchi, K., Yamamura, S., Prinetti, A., Handa, K., Hakomori, S.: GM3-enriched microdomain involved in cell adhesion and signal transduction through carbohydrate-carbohydrate interaction in mouse melanoma B16 cells. J. Biol. Chem. 273, 9130–9138 (1998)

    Article  PubMed  CAS  Google Scholar 

  9. Yamamura, S., Handa, K., Hakomori, S.: A close association of GM3 with c-Src and Rho in GM3-enriched microdomains at the B16 melanoma cell surface membrane: a preliminary note. Biochem. Biophys. Res. Commun. 236, 218–222 (1997)

    Article  PubMed  CAS  Google Scholar 

  10. Okada, Y., Mugnai, G., Bremer, E.G., Hakomori, S.: Glycosphingolipids in detergent-insoluble substrate attachment matrix (DISAM) prepared from substrate attachment material (SAM). Their possible role in regulating cell adhesion. Exp. Cell Res. 155, 448–456 (1984)

    CAS  Google Scholar 

  11. Simons, K., Ikonen, E.: Functional rafts in cell membranes. Nature 387, 569–572 (1997)

    Article  PubMed  CAS  Google Scholar 

  12. Iwabuchi, K., Nagaoka, I.: Lactosylceramide-enriched glycosphingolipid signaling domain mediates superoxide generation from human neutrophils. Blood 100, 1454–1464 (2002)

    PubMed  CAS  Google Scholar 

  13. Mukherjee, S., Maxfield, F.R.: Membrane domains. Annu. Rev. Cell Dev. Biol. 20, 839–866 (2004)

    Article  PubMed  CAS  Google Scholar 

  14. Arai, T., Bhunia, A.K., Chatterjee, S., Bulkley, G.B.: Lactosylceramide stimulates human neutrophils to upregulate Mac-1, adhere to endothelium, and generate reactive oxygen metabolites in vitro. Circ Res 82, 540–547 (1998)

    PubMed  CAS  Google Scholar 

  15. Bhunia, A.K., Han, H., Snowden, A., Chatterjee, S.: Redox-regulated signaling by lactosylceramide in the proliferation of human aortic smooth muscle cells. J. Biol. Chem. 272, 15642–15649 (1997)

    Article  PubMed  CAS  Google Scholar 

  16. Iwamoto, T., Fukumoto, S., Kanaoka, K., Sakai, E., Shibata, M., Fukumoto, E., Inokuchi Ji, J., Takamiya, K., Furukawa, K., Furukawa, K., Kato, Y., Mizuno, A.: Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand. J. Biol. Chem. 276, 46031–46038 (2001)

    Article  PubMed  CAS  Google Scholar 

  17. Gong, N., Wei, H., Chowdhury, S.H., Chatterjee, S.: Lactosylceramide recruits PKCalpha/epsilon and phospholipase A2 to stimulate PECAM-1 expression in human monocytes and adhesion to endothelial cells. Proc Natl Acad Sci USA 101, 6490–6495 (2004)

    Article  PubMed  CAS  Google Scholar 

  18. Sharma, D.K., Brown, J.C., Cheng, Z., Holicky, E.L., Marks, D.L., Pagano, R.E.: The glycosphingolipid, lactosylceramide, regulates beta1-integrin clustering and endocytosis. Cancer Res. 65, 8233–8241 (2005)

    Article  PubMed  CAS  Google Scholar 

  19. Abul-Milh, M., Paradis, S.E., Dubreuil, J.D., Jacques, M.: Binding of Actinobacillus pleuropneumoniae lipopolysaccharides to glycosphingolipids evaluated by thin-layer chromatography. Infect. Immun. 67, 4983–4987 (1999)

    PubMed  CAS  Google Scholar 

  20. Angstrom, J., Teneberg, S., Milh, M.A., Larsson, T., Leonardsson, I., Olsson, B.M., Halvarsson, M.O., Danielsson, D., Naslund, I., Ljungh, A., Wadstrom, T., Karlsson, K.A.: The laactosylceramide binding specificity of Helicobacter pylori. Glycobiology 8, 297–309 (1998)

    Article  PubMed  CAS  Google Scholar 

  21. Hahn, P.Y., Evans, S.E., Kottom, T.J., Standing, J.E., Pagano, R.E., Limper, A.H.: Pneumocystis carinii cell wall beta-glucan induces release of macrophage inflammatory protein-2 from alveolar epithelial cells via a lactosylceramide-mediated mechanism. J. Biol. Chem. 278, 2043–2050 (2003)

    Article  PubMed  CAS  Google Scholar 

  22. Karlsson, K.A.: Animal glycolipids as attachment sites for microbes. Chem. Phys. Lipids 42, 153–172 (1986)

    Article  PubMed  CAS  Google Scholar 

  23. Sato, T., Iwabuchi, K., Nagaoka, I., Adachi, Y., Ohno, N., Tamura, H., Seyama, K., Fukuchi, Y., Nakayama, H., Yoshizaki, F., Takamori, K., Ogawa, H.: Induction of human neutrophil chemotaxis by Candida albicans-derived beta-1,6-long glycoside side-chain-branched beta-glucan. J. Leukoc. Biol. 80, 204–211 (2006)

    Article  PubMed  CAS  Google Scholar 

  24. Saukkonen, K., Burnette, W.N., Mar, V.L., Masure, H.R., Tuomanen, E.I.: Pertussis toxin has eukaryotic-like carbohydrate recognition domains. Proc Natl Acad Sci USA 89, 118–122 (1992)

    Article  PubMed  CAS  Google Scholar 

  25. Zimmerman, J.W., Lindermuth, J., Fish, P.A., Palace, G.P., Stevenson, T.T., DeMong, D.E.: A novel carbohydrate-glycosphingolipid interaction between a beta-(1–3)-glucan immunomodulator, PGG-glucan, and lactosylceramide of human leukocytes. J. Biol. Chem. 273, 22014–22020 (1998)

    Article  PubMed  CAS  Google Scholar 

  26. Greenberg, S., Grinstein, S.: Phagocytosis and innate immunity. Curr. Opin. Immunol. 14, 136–145 (2002)

    Article  PubMed  CAS  Google Scholar 

  27. Brown, D.A., Rose, J.K.: Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 68, 533–544 (1992)

    Article  PubMed  CAS  Google Scholar 

  28. Parkin, E.T., Turner, A.J., Hooper, N.M.: Differential effects of glycosphingolipids on the detergent-insolubility of the glycosylphosphatidylinositol-anchored membrane dipeptidase. Biochem. J. 358, 209–216 (2001)

    Article  PubMed  CAS  Google Scholar 

  29. Palestini, P., Allietta, M., Sonnino, S., Tettamanti, G., Thompson, T.E., Tillack, T.W.: Gel phase preference of ganglioside GM1 at low concentration in two-component, two-phase phosphatidylcholine bilayers depends upon the ceramide moiety. Biochim. Biophys. Acta. 1235, 221–230 (1995)

    Article  PubMed  Google Scholar 

  30. Acquotti, D., Sonnino, S.: Use of nuclear magnetic resonance spectroscopy in evaluation of ganglioside structure, conformation, and dynamics. Methods Enzymol. 312, 247–272 (2000)

    PubMed  CAS  Google Scholar 

  31. Mauri, L., Casellato, R., Kirschner, G., Sonnino, S.: A procedure for the preparation of GM3 ganglioside from GM1-lactone. Glycoconj. J. 16, 197–203 (1999)

    Article  PubMed  CAS  Google Scholar 

  32. Tokyokuni, T., Nisar, M., Dean, B., Hakomori, S.: A facile and regiospecific titration of sphingosine: synthesis of (2S,3R,4E)-2-amino-4-octadecene-1,3-diol-1-3H. J, Labeled Compd. Radiopharm. 29, 567–574 (1991)

    Article  Google Scholar 

  33. Vaissiere, C., Le Cabec, V., Maridonneau-Parini, I.: NADPH oxidase is functionally assembled in specific granules during activation of human neutrophils. J. Leukoc. Biol. 65, 629–634 (1999)

    PubMed  CAS  Google Scholar 

  34. Someya, A., Nagaoka, I., Iwabuchi, K., Yamashita, T.: Comparison of O2(-)-producing activity of guinea-pig eosinophils and neutrophils in a cell-free system. Comp. Biochem. Physiol. [B] 100, 25–30 (1991)

    Article  CAS  Google Scholar 

  35. Brkovic, A., Pelletier, M., Girard, D., Sirois, M.G.: Angiopoietin chemotactic activities on neutrophils are regulated by PI-3K activation. J. Leukoc. Biol. 81, 1093–1101 (2007)

    Article  PubMed  CAS  Google Scholar 

  36. Kurihara, H., Anderson, J.M., Farquhar, M.G.: Increased Tyr phosphorylation of ZO-1 during modification of tight junctions between glomerular foot processes. Am. J. Physiol. 268, F514–524 (1995)

    PubMed  CAS  Google Scholar 

  37. Dimmock, E., Franks, D., Glauert, A.M.: The location of blood group antigen A on cultured rabbit kidney cells as revealed by ferritin-labelled antibody. J. Cell Sci. 10, 525–533 (1972)

    PubMed  CAS  Google Scholar 

  38. Munn, E.A., Bachmann, L., Feinstein, A.: Structure of hydrated immunoglobulins and antigen-antibody complexes. Electron microscopy of spray-freeze-etched specimens. Biochim. Biophys. Acta. 625, 1–9 (1980)

    CAS  Google Scholar 

  39. Parkhouse, R.M., Askonas, B.A., Dourmashkin, R.R.: Electron microscopic studies of mouse immunoglobulin M; structure and reconstitution following reduction. Immunology 18, 575–584 (1970)

    PubMed  CAS  Google Scholar 

  40. Plowman, S.J., Muncke, C., Parton, R.G., Hancock, J.F.: H-ras, K-ras, and inner plasma membrane raft proteins operate in nanoclusters with differential dependence on the actin cytoskeleton. Proc. Natl. Acad. Sci. USA 102, 15500–15505 (2005)

    Article  PubMed  CAS  Google Scholar 

  41. Macher, B.A., Klock, J.C.: Isolation and chemical characterization of neutral glycosphingolipids of human neutrophils. J. Biol. Chem. 255, 2092–2096 (1980)

    PubMed  CAS  Google Scholar 

  42. Symington, F.W., Murray, W.A., Bearman, S.I., Hakomori, S.: Intracellular localization of lactosylceramide, the major human neutrophil glycosphingolipid. J. Biol. Chem. 262, 11356–11363 (1987)

    PubMed  CAS  Google Scholar 

  43. Kniep, B., Skubitz, K.M.: Subcellular localization of glycosphingolipids in human neutrophils. J. Leukoc. Biol. 63, 83–88 (1998)

    PubMed  CAS  Google Scholar 

  44. Rajendran, L., Simons, K.: Lipid rafts and membrane dynamics. J. Cell Sci. 118, 1099–1102 (2005)

    Article  PubMed  CAS  Google Scholar 

  45. Resh, M.D.: Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim. Biophys. Acta 1451, 1–16 (1999)

    Article  PubMed  CAS  Google Scholar 

  46. Kobayashi, T., Shinnoh, N., Goto, I., Kuroiwa, Y., Okawauchi, M., Sugihara, G., Tanaka, M.: Galactosylceramide- and lactosylceramide-loading studies in cultured fibroblasts from normal individuals and patients with globoid cell leukodystrophy (Krabbe’s disease) and GM1-gangliosidosis. Biochim. Biophys. Acta. 835, 456–464 (1985)

    PubMed  CAS  Google Scholar 

  47. Martin, S.F., Williams, N., Chatterjee, S.: Lactosylceramide is required in apoptosis induced by N-Smase. Glycoconj. J. 23, 147–157 (2006)

    Article  PubMed  CAS  Google Scholar 

  48. Nijhuis, E., Lammers, J.W., Koenderman, L., Coffer, P.J.: Src kinases regulate PKB activation and modulate cytokine and chemoattractant-controlled neutrophil functioning. J. Leukoc. Biol. 71, 115–124 (2002)

    PubMed  CAS  Google Scholar 

  49. Kusumi, A., Koyama-Honda, I., Suzuki, K.: Molecular dynamics and interactions for creation of stimulation-induced stabilized rafts from small unstable steady-state rafts. Traffic 5, 213–230 (2004)

    Article  PubMed  CAS  Google Scholar 

  50. Zuvic-Butorac, M., Muller, P., Pomorski, T., Libera, J., Herrmann, A., Schara, M.: Lipid domains in the exoplasmic and cytoplasmic leaflet of the human erythrocyte membrane: a spin label approach. Eur. Biophys. J. 28, 302–311 (1999)

    Article  PubMed  CAS  Google Scholar 

  51. Prinetti, A., Chigorno, V., Prioni, S., Loberto, N., Marano, N., Tettamanti, G., Sonnino, S.: Changes in the lipid turnover, composition, and organization, as sphingolipid-enriched membrane domains, in rat cerebellar granule cells developing in vitro. J. Biol. Chem. 276, 21136–21145 (2001)

    Article  PubMed  CAS  Google Scholar 

  52. Allende, D., Vidal, A., McIntosh, T.J.: Jumping to rafts: gatekeeper role of bilayer elasticity. Trends Biochem. Sci. 29, 325–330 (2004)

    Article  PubMed  CAS  Google Scholar 

  53. Tanford, C.: The Hydrophobic Effect: Formation of Micelles and Biological Membranes. Ohn Wiley and Sons Inc, New York (1980)

    Google Scholar 

  54. Grant, C.W., Mehlhorn, I.E., Florio, E., Barber, K.R.: A long chain spin label for glycosphingolipid studies: transbilayer fatty acid interdigitation of lactosyl ceramide. Biochim. Biophys. Acta 902, 169–177 (1987)

    Article  PubMed  CAS  Google Scholar 

  55. Li, X.M., Momsen, M.M., Brockman, H.L., Brown, R.E.: Lactosylceramide: effect of acyl chain structure on phase behavior and molecular packing. Biophys. J. 83, 1535–1546 (2002)

    Article  PubMed  CAS  Google Scholar 

  56. Fra, A.M., Masserini, M., Palestini, P., Sonnino, S., Simons, K.: A photo-reactive derivative of ganglioside GM1 specifically cross-links VIP21-caveolin on the cell surface. FEBS Lett. 375, 11–14 (1995)

    Article  PubMed  CAS  Google Scholar 

  57. Prinetti, A., Marano, N., Prioni, S., Chigorno, V., Mauri, L., Casellato, R., Tettamanti, G., Sonnino, S.: Association of Src-family protein tyrosine kinases with sphingolipids in rat cerebellar granule cells differentiated in culture. Glycoconj. J. 17, 223–232 (2000)

    Article  PubMed  CAS  Google Scholar 

  58. Palestini, P., Pitto, M., Tedeschi, G., Ferraretto, A., Parenti, M., Brunner, J., Masserini, M.: Tubulin anchoring to glycolipid-enriched, detergent-resistant domains of the neuronal plasma membrane. J. Biol. Chem. 275, 9978–9985 (2000)

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We are grateful to Dr. Sen-itiroh Hakomori (University of Washington) for his encouragement and invaluable comments throughout this study. We thank Dr. Hiroshi Tamura (Seikagaku Corporation) and Drs. Yoshiyuki Adachi and Naohito Ohno (Tokyo University of Pharmacy and Life Science) for providing Candida albicans-derived β-glucan and Sparassis crispa-derived β-glucan, respectively. We also thank Dr. Irwin D. Bernstein at Fred Hutchinson Cancer Research Center, Seattle, WA, USA, for important contributions.

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Authors and Affiliations

  1. Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu-shi, Chiba, 279-0021, Japan

    Kazuhisa Iwabuchi, Hitoshi Nakayama, Fumiko Yoshizaki, Kenji Takamori & Hideoki Ogawa

  2. Infectious Control Nursing, Juntendo University Graduate School of Health Care and Nursing, Chiba, Japan

    Kazuhisa Iwabuchi

  3. Center of Excellence on Neurodegenerative Diseases; Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milano, Milan, Italy

    Alessandro Prinetti, Sandro Sonnino & Laura Mauri

  4. Sphingolipid Functions Laboratory, Frontier Research System, RIKEN, Saitama, Japan

    Toshihide Kobayashi & Kumiko Ishii

  5. Division of Proteomics and Biomolecular Science, BioMedical Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Naoko Kaga & Kimie Murayama

  6. Department of Anatomy, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Hidetake Kurihara

  7. Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Isao Nagaoka

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  1. Kazuhisa Iwabuchi
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Correspondence to Kazuhisa Iwabuchi.

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This study was supported in part by a grant-in-aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (16017293) to K.I., by COFIN-PRIN 2004 to A.P., and by “High-Tech Research Center” Project for Private Universities: matching fund subsidy.

An erratum to this article can be found at http://dx.doi.org/10.1007/s10719-008-9110-3

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Iwabuchi, K., Prinetti, A., Sonnino, S. et al. Involvement of very long fatty acid-containing lactosylceramide in lactosylceramide-mediated superoxide generation and migration in neutrophils. Glycoconj J 25, 357–374 (2008). https://doi.org/10.1007/s10719-007-9084-6

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