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Polymorphonuclear Neutrophil Dysfunctions in Streptozotocin-induced Type 1 Diabetic Rats

  • Nabi, A.H.M. Nurun (Department of Biochemistry and Molecular Biology, University of Dhaka) ;
  • Islam, Laila N. (Department of Biochemistry and Molecular Biology, University of Dhaka) ;
  • Rahman, Mohanmmad Mahfuzur (Department of Biochemistry and Molecular Biology, University of Dhaka) ;
  • Biswas, Kazal Boron (Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders)
  • Published : 2005.11.30

Abstract

Since conflicting results have been reported on non-specific immune response in type 1 diabetes, this study evaluates polymorphonuclear neutrophil (PMN) functions in the infection free Long Evan diabetic rats (type 1) by using tests that include: polarization assay, phagocytosis of baker's yeasts (Saccharomyces cerevisiae) and nitroblue tetrazolium (NBT) dye reduction. Polarization assay showed that neutrophils from diabetic rats were significantly activated at the basal level compared to those from the controls (p < 0.001). After PMN activation with N-formyl-methionyl-leucyl-phenylalanine (FMLP), control neutrophils were found to be more polarized than those of the diabetic neutrophils and the highest proportions of polarization were found to be 67% and 57% at $10^{-7}\;M$ FMLP, respectively. In the resting state, neutrophils from the diabetic rats reduced significantly more NBT dye than that of the controls (p < 0.001). The percentages of phagocytosis of opsonized yeast cells by the neutrophils from control and diabetic rats were 87% and 61%, respectively and the difference was statistically significant (p < 0.001). Evaluation of the phagocytic efficiency of PMNs revealed that control neutrophils could phagocytose $381{\pm}17$ whereas those from the diabetic rats phagocytosed $282{\pm}16$ yeast cells, and the efficiency of phagocytosis varied significantly (p < 0.001). Further, both the percentages of phagocytosis and the efficiency of phagocytosis by the diabetic neutrophils were inversely related with the levels of their corresponding plasma glucose (p = 0.02; r = -0.498 and p < 0.05; r = -0.43, respectively), which indicated that increased plasma glucose reduced the phagocytic ability of neutrophils. Such relationship was not observed with the control neutrophils. These data clearly indicate that PMN functions are altered in the streptozotocin (STZ) - induced diabetic rats, and hyperglycemia may be the cause for the impairment of their functions leading to many infectious episodes.

Keywords

References

  1. Albanyan, E. A., Vallejo, J. G., Smith, C. W. and Edwards, M. S. (2000) Nonopsonic binding of type III group B Streptococci to human neutrophils induces interleukin-8 release mediated by the p38 mitogen-activated protein kinase pathway. Infect. Immun. 68, 2053-2060 https://doi.org/10.1128/IAI.68.4.2053-2060.2000
  2. Billinati-Pires, R., Carneiro-Sampaio, M. M. and Colletto, G. M. (1992) Functional evaluation of human neutrophils. Is the bactericidal activity correlated with nitroblue tetrazolium reduction? J. Invest. Allergol. Clin. Immunol. 2, 146-153
  3. Biswas, S. K., Bhewla, A. P., Upadhyay, A. U., George, A. and Nath, N. (1993) Status of nitric oxide free radicals in diabetic neutrophils: effect of diabetic serum factor on the generation of these species in normal neutrophils and their relation to lysosomal degranulation. Indian J. Biochem. Biophys. 30, 193- 196
  4. Botelho, R. J., Tapper, H., Furuya, W., Mojdami, D. and Grinstein, S. (2002) FcgR-mediated phagocytosis stimulates localized pinocytosis in human neutrophils. J. Immunol. 169, 4423-4429 https://doi.org/10.4049/jimmunol.169.8.4423
  5. Coopan, R. (1985) Infection and diabetes; in Joslin's Diabetes Mellitus, Marbell L. P., Krall, R. F. and Brandley, A. R. (eds.), pp. 737-747, Williams and Wilkins, Lea & Febiger, Philadelphia, USA
  6. Csato, M., Dobozy, A. and Simon, N. (1980) Study of phagocytic function with a quantitative nitroblue-tetrazolium (NBT) dye reduction tests in diabetes mellitus. Arch. Dermatol. Res. 268, 283-288 https://doi.org/10.1007/BF00404290
  7. Cywes, C., Hoppe, H. C., Daffe, M. and Ehlers, M. R. W. (1997) Nonopsonic binding of Mycobacterium tuberculosis to complement receptor type 3 is mediated by capsular polysaccharides and is strain dependent. Infect. Immun. 65, 4258-4266
  8. Delamaire, M., Maugendre, D., Moreno, M., LeGoff, M. C., Allanic, H. and Genetet, B. (1995) Exploration of the various steps of polymorphonuclear neutrophil function in diabetic patients. J. Mal. Vasc. 20, 107-112
  9. Dziatkowiak, H., Kowalska, M. and Denys, A. (1982) Phagocytic and bactericidal activity of granulocytes in diabetic children. Diabetes 31, 1041-1043 https://doi.org/10.2337/diabetes.31.12.1041
  10. Eastabrook, M. M., Zhou, D. and Apicella, M. A. (1998) Nonopsonic phagocytosis of group C Neisseria meningitis by human neutrophils. Infect. Immun. 66, 1028-1036
  11. Ehlers, M. R. W. (2000) CR3: a general purpose adhesionrecognition receptor essential for innate immunity. Microbes Infect. 2, 289-294 https://doi.org/10.1016/S1286-4579(00)00299-9
  12. Gallacher, S. J., Thomson, G., Fraser, W. D., Fisher, B. M. and Gemmell, C. G. (1995) Neutrophil bactericidal functions in diabetes mellitus: evidence for association with blood glucose control. Diabetic Med. 12, 916-920 https://doi.org/10.1111/j.1464-5491.1995.tb00396.x
  13. Hetland, G. and Wiker, H. G. (1994) Antigen 85C on Mycobacterium bovis, BCG and M. tuberculosis promotes monocyte-CR3-mediated uptake of microbeads coated with mycobacterial products. Immunology 82, 445-449
  14. Hostetter, M. K. (1990) handicaps to host defence. Effects of hyperglycemia on C3 and Candida albicans. Diabetes 39, 271- 275 https://doi.org/10.2337/diabetes.39.3.271
  15. Islam, L. N., Islam, K. S., Kabir, E. M., Hossain, M. S., Nabi, A. H. M. N. and Banik, N. G. (2000) Impaired neutrophil functions in diabetes mellitus. Bangladesh J. Biochem. 6, 45- 59
  16. Islam, L. N. and Nabi, A. H. M. N. (2003) Endotoxins of Enteric Pathogens Modulate the Functions of Human Neutrophils and Lymphocytes. J. Biochem. Mol. Biol. 36, 565-571 https://doi.org/10.5483/BMBRep.2003.36.6.565
  17. Islam, L. N. and Wilkinson, P. C. (1988) Chemotactic factor induced polarization, receptor redistribution and locomotion of human blood monocytes. Immunology 64, 501-507
  18. Mahenthiralingam, E. and Speert, D. P. (1995) Nonopsonic phagocytosis of Pseudomonas aeruginosa by macrophages and polymorphonuclear leukocytes requires the presence of bacterial flagellum. Infect. Immun. 63, 4519-4523
  19. Marhoffer, W., Stein, M., Maeser, E. and Federlin, k. (1992) Impairment of polymorphonuclear leukocyte function and diabetes mellitus. Diabetes Care 15, 256-260 https://doi.org/10.2337/diacare.15.2.256
  20. Marhoffer, W., Stein, M., Schleinkofer, L. and Federlin, k. (1993) Evidence of ex vivo and in vitro impaired neutrophil oxidative burst and phagocytic capacity in type 1 diabetes mellitus. Diabetes Res. Clin. Pract. 19, 183-188 https://doi.org/10.1016/0168-8227(93)90112-I
  21. Nabi, A. H. M. N. and Islam, L. N. (2001) Study of the functions of human neutrophils in response to Klebsiella pneumoniae LPS. Dhaka Univ. J. Biol. Sci. 10, 59-68
  22. Oldenborg, P. A. and Sehlin, J. (1997) D-glucose but not insulin induces N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu- Phe)-induced shape changes in suspended human neutrophils. Biosci. Rep. 17, 475-486 https://doi.org/10.1023/A:1027347904512
  23. Ortmeyer, J. and Mohsenin, V. (1996) Inhibition of phospholipase D and superoxide generation by glucose in diabetic neutrophils. Life Sci. 59, 255-262 https://doi.org/10.1016/0024-3205(96)00284-6
  24. Peyron, P., Bordier, C., N'Diaye, E. and Maridonneau-Parini, I. (2000) Nonopsonic phagocytosis of Mycobacterium kansasii by human neutrophils depends on cholesterol and Is mediated by CR3 associated with glycosylphosphatidylinositol-anchored proteins. J. Immunol. 165, 5186-5191 https://doi.org/10.4049/jimmunol.165.9.5186
  25. Reeves, W. G. and Wilson, R. M. (1992) Infection, immunity and diabetes; in International Textbook of Diabetes Mellitus, Alberti, K. G. M. M., De Fronzo, R. A., Kenn, H. and Zimmet, P. (eds.), p. 1165, John Wiley and Son, New York, USA
  26. Ross, G. D., Cain, J. A. and Lachmann, P. J. (1985.) Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin and functions as a receptor for zymosan and rabbit erythrocytes as well as receptor for iC3b. J. Immunol. 134, 3307-3315
  27. Sato, N., Shimizu, H., Suwa, K., Shimomura, Y., Mori, M. and Kobayashi, I. (1992) Myeloperoxidase activity and generation of active oxygen species in leukocytes from poorly controlled diabetic patients. Diabetes Care 15, 1050-1052 https://doi.org/10.2337/diacare.15.8.1050
  28. Sato, N., Shimizu, H., Suwa, K., Uehara, Y., Shimomura, Y., Kobayashi, I. and Kobayashi, S. (1992) Reduced ability of neutrophils to produce active oxygen species in streptozotocininduced diabetic rats. Exp. Clin. Endocrinol. 99, 31-33 https://doi.org/10.1055/s-0029-1211128
  29. Sato, N., Kashima, K., Shimizu, H., Uehara, U., Shimomura, S. and Mori, M. (1993) Hypertonic glucose inhibits the production of oxygen-derived free radicals by rat neutrophils. Life Sci. 51, 113-118 https://doi.org/10.1016/0024-3205(92)90004-9
  30. Sengelov, H. (1995) Complement receptors in neutrophils. Crit. Rev. Immunol. 15, 107-131 https://doi.org/10.1615/CritRevImmunol.v15.i2.10
  31. Serlenga, E., Garofalo, A. R., De Pergola, G., Ventura, M. T., Tortorella, C. and Antonaci, S. (1993) Polymorphonuclear cellmediated phagocytosis and superoxide anion release in insulindependent diabetes mellitus. Cytobios. 74, 189-195
  32. Shah, S. V., Wallin, J. D. and Eilen, S. D. (1983) Chemiluminescence and superoxide anion production by leukocytes from diabetic patients. J. Clin. Endocrinol. Metab. 57, 402-409 https://doi.org/10.1210/jcem-57-2-402
  33. Shields, J. M. and Haston, W. S. (1985) Behaviour of neutrophil leukocytes in uniform concentrations of chemotactic factors: contraction waves, cell polarity and persistence. J. Cell Sci. 74, 79-93
  34. Weirusz-Wysocka, B., Wysocki, H., Siekierka, H., Wykretowicz, A., Szczepanik, A. and Klimas, R. (1987) Evidence of polymorphonuclear neutrophils (PMN) activation in patients with insulin-dependent diabetes mellitus. J. Leukoc. Biol. 42, 519-523 https://doi.org/10.1002/jlb.42.5.519
  35. Wilson, R. M. and Reeves, W. G. (1986) Neutrophil phagocytosis and killing in insulin-dependent diabetes. Clin. Exp. Immunol. 63, 478-484

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