Abstract
Gangliosides are known to be differentiation-inducing molecules in mammalian stem cells. We studied the interaction between the molecular structure of glycosphingolipids (GSLs) and their promoting mechanisms of the phagocytic processes in human polymorphonuclear leukocytes (PMN). The effect of various gangliosides from mammalian tissues on adhesion, phagocytosis, phagosome–lysosome (P–L) fusion and superoxide anion production was examined by human PMN using heat-killed cells of Staphylococcus aureus coated with GSLs. Gangliosides GM3, GD1a, GD3 and GT1b showed a marked stimulatory effect on the phagocytosis and P–L fusion in a dose-dependent manner, while ganglioside GM1, asialo GM1 and neutral GSLs did not. The relative phagocytic rate of ganglioside GM3-coated S. aureus was the highest among the tested GSLs. Both P–L fusion rate and phagocytosis of S. aureus were elevated significantly when coated with ganglioside GD1a, GD3 or GT1b, and GT1b gave a five times higher rate than that of the non-coated control. These results suggest that the terminal sialic acid moiety is essential for the enhancement of phagocytosis and that the number of sialic acid molecules in the ganglioside is related to the enhancement of the P–L fusion process. On the other hand, the superoxide anion release from PMN was not affected by ganglioside GM2, GM3, GD1a or GT1b. Furthermore, to clarify the trigger or the signal transduction mechanism of phagocytic processes, we examined the effect of protein kinase inhibitors such as H-7, staurosporine (protein kinase C inhibitor), H-89 (protein kinase A inhibitor), genistein (tyrosine kinase inhibitor), ML-7 (myosin light chain kinase inhibitor), and KN-62 (Ca2+/calmodulin-dependent protein kinase II inhibitor) on ganglioside-induced phagocytosis. H-7, staurosporine and KN-62 inhibited ganglioside-induced phagocytosis in the range of concentration without cell damage, while H-89, genistein and ML-7 did not. Moreover, H-7 and KN-62 inhibited ganglioside-induced P–L fusion. These results suggest that protein kinase C and Ca2+/calmodulin-dependent protein kinase II may be involved in the induction of phagocytosis and P–L fusion stimulated by gangliosides.
Similar content being viewed by others
References
Coleman DL, Morrison DC, Ryan JL (1986) Cellular Immunol 100: 288-99.
Melikyan GB, Matinyan NS, Arakelian VB (1990) Biochim Biophys Acta 1030: 11-15.
Nojiri H, Kitagawa S, Nakamura M, Kirito K, Enomoto Y, Saito M (1988) J Biol Chem 263: 7443-46.
Riedl M, Forster O, Rumpold H, BernheimerH (1982) J Immunol 128: 1205-10.
Karlsson KA (1989) Annu Rev Biochem 58: 309-50.
Ofek I, Sharon N (1990) Curr Top Microbiol Immunol 151: 91-113.
Ladisch S, Becker H, Ulsh L (1992) Biochim Biophys Acta 1125: 180-88.
Ladisch S, Hasegawa A, Li R, Kiso M (1994) Biochem Biophys Res Commun 203: 1102-9.
Ladisch S, Li R, Olson E (1994) Proc Natl Acad Sci 91: 1974-78. Effect of gangliosides on phagocytosis and phagosome-lysosome fusion 713
Ladisch S, Hasegawa A, Li R, Kiso M (1995) Biochemistry 34: 1197-202.
Tiemeyer M, Swank-Hill P, Schnaar RL (1990) J Biol Chem 265: 11990-99.
Saito M (1993) Adv Lipid Res 25: 303-27.
Miyazaki Y, Oka S, Yamaguchi S, Mizuno S, Yano I (1995) J Biochem 118: 271-77.
Yamaguchi S, Miyazaki Y, Oka S, Yano I (1996) FEMS Immunol Med Microbiol 13: 107-111.
Kitagawa S, Ohta M, Nojiri H, Kakinuma K, Saito M, Takaku F, Miura Y (1984) J Clin Invest 73: 1062-71.
Miyazaki Y, Oka S, Hara-Hotta H, Yano I (1993) FEMS Immunol Med Microbiol 6: 265-72.
Hidaka H, Inagaki M, Kawamoto S, Sasaki Y (1984) Biochemistry 23: 5036-41.
Gross JL, Herblin WF, Do UH, Pounds JS, Buenaga LJ, Stephens LE (1990) Biochem Pharmacol 40: 343-50.
Chijiwa T, Mishima A, Hagiwara M, Sano M, Hayashi K, Inoue T, Naito K, Toshioka T, Hidaka H (1990) J Biol Chem 265: 5267-72.
Linassier C, Pierre M, Le Pecq JB, Pierre J (1990) Biochem Pharmacol 39: 187-93.
Saitoh M, Ishikawa T, Matsushima S, Naka M, Hidaka H (1987) J Biol Chem 262: 7796-801
Tokumitsu H, Chijiwa T, Hagiwara M, Mizutani A, Terasawa M, Hidaka H (1990) J Biol Chem 265: 4315-20.
Van Oss CJ (1978) Ann Rev Microbiol 32:19-39.
Brandley BK, Kiso M, Abbas S, Nikrad P, Srivasatava O, Foxall C, Oda Y, Hasegawa A (1993) Glycobiology 3: 633-39.
Yuen CT, Bezouška K, O'Brien J, Stoll M, Lemoine R, Lubineau A, Kiso M, Hasegawa A, Bockovich NJ, Nicolaou KC, Feizi T (1994) JBiol Chem 269: 1595-98.
Zheng L, Zomerdijk TPL, Aarnoudse C, Furth RV, Nibbering PH (1995) J Immunol 155: 776-84.
Gresham HD, Zheleznyak A, Mormol JS, Brown EJ (1990) J Biol Chem 265: 7819-26.
Tanimura M, Kobuchi H, Utsumi T, Yoshioka T, Kataoka S, Fujita Y, Utsumi K (1992) Biochem Pharmacol 44: 1045-52.
Takai Y, Sasaki T, Tanaka K, Nakanishi H (1995) Trends in Biochemical Sciences 20: 227-31.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yamaguchi, S., Miyazaki, Y., Oka, S. et al. Stimulatory effect of gangliosides on phagocytosis, phagosome–lysosome fusion, and intracellular signal transduction system by human polymorphonuclear leukocytes. Glycoconj J 14, 707–714 (1997). https://doi.org/10.1023/A:1018517400380
Issue Date:
DOI: https://doi.org/10.1023/A:1018517400380