Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
권호 표지

Neutrophil Apoptosis and $H_2O_2$ Release by LPS in Diabetics

내독소로 자극된 당뇨환자의 중성구에서 기획성 세포사멸과 과산화수소 분비능

  • Seo, Ki Hyun (Department of Internal Medicine, Soonchunhyang University College of Medicine, Clinical research institute) ;
  • Na, Joo Ock (Department of Internal Medicine, Soonchunhyang University College of Medicine, Clinical research institute) ;
  • Moon, Seung Hyug (Department of Internal Medicine, Soonchunhyang University College of Medicine, Clinical research institute) ;
  • Uh, Soo Taek (Department of Internal Medicine, Soonchunhyang University College of Medicine, Clinical research institute) ;
  • Kim, Yong Hoon (Department of Internal Medicine, Soonchunhyang University College of Medicine, Clinical research institute) ;
  • Park, Choon Sik (Department of Internal Medicine, Soonchunhyang University College of Medicine, Clinical research institute)
  • 서기현 (순천향대학교 의과대학 내과학 교실, 임상의학연구소) ;
  • 나주옥 (순천향대학교 의과대학 내과학 교실, 임상의학연구소) ;
  • 문승혁 (순천향대학교 의과대학 내과학 교실, 임상의학연구소) ;
  • 어수택 (순천향대학교 의과대학 내과학 교실, 임상의학연구소) ;
  • 김용훈 (순천향대학교 의과대학 내과학 교실, 임상의학연구소) ;
  • 박춘식 (순천향대학교 의과대학 내과학 교실, 임상의학연구소)
  • Received : 2004.03.03
  • Accepted : 2004.08.18
  • Published : 2004.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background : Bacterial infections in diabetic patients are an important cause of increased morbidity and mortality. It has been reported that bacterial infections in diabetics showed more impaired PMN functions such as reduced PMN respiratory burst and decreased microbicidal activity in inflammed tissues. Also, apoptosis(programmed cell death) is postulated to be a key mechanism for neutrophil elimination. It is very important that PMN apoptosis keeps the balance from an area of inflammation. Actuallly, as little was known about PMN apoptosis and respiratory burst in diabetes, we investigated PMN apoptosis and hydrogen peroxide production after endotoxin exposure. Methods : Peripheral venous blood samples were collected by routine venipuncture from healthy volunteers and diabetics to harvest neutrophils. We respectively measured the PMN apoptosis, the production of hydrogen peroxide, and the cell viability. Results : Normal neutrophils showed a tendency to decreased apoptosis after endotoxin treatment. In patients with diabetes, PMN apoptosis was significantly decreased compared with healthy controls. In addition, the LPS-induced neutrophils in diabetics demonstrated more decreased apoptosis. However, the production of hydrogen peroxide was not different between groups. Conclusion : These observations suggest that the decreased PMN apoptosis in diabetics with endotoxin exposure may also affect the increased susceptibility and severity of infections.

배 경 : 세균 감염 시 이환율과 사망률이 증가한다고 알려져 있는 당뇨에서 염증 조직 내 활성 산소 기능과 세균능 감소를 보이는 중성구의 기능 이상이 잘 알려져 있다. 또한, 기획성 세포사멸이 중성구 제거에 중요한 역할을 한다고 알려져 있다. 중성구의 기획성 세포사멸은 염증 조직 내I 균형을 유지하는 데 중요하다. 실제 당뇨병에서 중성구의 기획성 세포사멸과 활성 산소에 대한 연구가 없는 실정으로 본 연구를 통해 당뇨에서 내독소 투여시 중성구의 기획성 세포사멸과 과산화수소 분비능을 알고자 하였다. 방 법 : 정상과 당뇨 환자의 전혈을 뽑아 중성구 만을 추출하여 내독소에 노출시킨 후 중성구의 기획성 세포사멸, 과산화수소 분비능, 생존율을 각각 측정하였다. 결 과 : 정상 중성구는 내독소 투여 후 기획성 세포사멸이 감소하는 경향을 보였다. 정상과 비교할 때 당뇨환자의 중성구는 기획성 세포사멸이 감소하였고 특히 내 독소를 투여한 군에서 더욱 감소하였다. 과산화수소 분비능의 차이는 보이지 않았다. 결 론 : 본 연구를 통해 당뇨환자에서 내독소 투여로 인한 중성구의 기획성 세포사멸 감소가 당뇨에서 중증 감염과 높은 사망률에 영향을 줄 것으로 사료된다.

Keywords

Acknowledgement

Supported by : 순천향대학교 임상의학연구소

References

  1. Cochrane CG. Immunologic tissue injury mediated by neutrophilic leukocytes. Adv Immunol. 1968;9:97-162
  2. Henson PM, Johnston RB Jr. Tissue injury in inflammation: oxidants, proteinases and cationic proteins. J Clin Invest. 1987;79:669-74
  3. Weiss SJ. Tissue destruction by neutrophils. N Engl J Med 1989;320:365-76
  4. Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson PM, and Haslett C. Macrophage phagocytosis of aging neutrophils in inflammation: programmedcell death in the neutrophil leads to recogntion by macrophages. J Clin Invest 1989;83:865-75
  5. Dransfield I, Stocks SC, Haslett C. Regulation of cell adhesion molecule expression and function associated with neutrophil apoptosis. Blood 1995;85: 3264-73
  6. Haslett C, Savill JS, Whyte MK, Stern M, Dransfield I, Meagher LC. Granulocyte apoptosis and the control of inflammation. Philos Trans R Soc Lond B Biol Sci1994;345:327-33
  7. Colotta F, ReF Polentarutti N, Sozzani S, Montobani A. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood 1992;80:2012-20
  8. Brach MA, deVos S, Gruss HJ, Herrmann F. Prolongation of survival of human polymorphonuclear neutrophils by granulocyte-macrophage colony-stimulating factor is caused by inhibition of programmed cell death. Blood 1992;80:2920-4
  9. Ymamoto C, Yoshida S, Taniguchi H Qin MH, Miyamoto H, Mizuguchi H. Lipopolysaccharide and granulocyte colony-stimulating factor delay neutrophilapoptosis and ingestion by guinea pig macrophages. Infect Immun 1993;61:1972-9
  10. Pericle F, Liu JH, Diaz JI, Blanchard DK, Wei S, Forni G, Djeu JY. Interleukin-2 prevention of apoptosis in human neutrophils. Eur J Immunol 1994;24:440-4
  11. Hachiya O, Takeda Y, Miyata H, Watanabe H,Yamashita T, Sendo F. Inhibition by bacterial lipo-polysaccharide of spontaneous and TNF $\alpha$-induced human neutrophil apoptosis in vitro. Microbiol Immunol 1995;39:715-23
  12. Haslett C. Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes. Clin Sci 1992;83:639-48
  13. Biffl WL, Moore EE, Moore FA, Barnett CC Jr. Interleukin-6 suppression of neutrophil apoptosis is neutro-phil concentration dependent. J Leukoc Biol1995;58:582-4
  14. Riley PA. Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 1994;65:27-33
  15. Lennon SV, Martin SJ, Cotter TG. Dose-dependent induction of apoptosis in human tumor cell lines by widely diverging stimuli. Cell Prolif 1991;24:203-14
  16. Larkin JG, Frier BM, Ireland JT. Diabetes mellitus and Infection. Postgrad Med J 1985;61:233-7
  17. Murphy DP, Tan JS, File TM Jr. Infectious complications in diabetic patients. Primary Care 1981;8:695-714
  18. Rayfield EJ, Ault MJ, Keusch GT. Brothers MJ, Nechemias CH, Smith H. Infection and diabetes: the case for glucose control. Am J Med 1982;72:439-50
  19. Wheat LJ. Infection and diabetes mellitus. Diabetes Care 1980;3:187-97
  20. Bagdade JD, Root RK, Bulger RJ. Impaired leukocyte function in patients with poorly controlled diabetes. Diabetes 1974;23:9-15
  21. Bagdade JD, Stewart M, Walters E. Impaired granulocyte adherence: a reversible defect in host defense in patients with poorly controlled diabetes.Diabetes 1978;27:677-81
  22. Marhoffer W, Stein M, Maeser E, Federhn K. Impaired of polymorphonuclear leukocyte function and metabolic control of diabetes. Diabetes Care 1992;15:256-60
  23. Glowacka E, Banasik M, Lewkowicz P, Tchorzewski H. The effect of LPS on neutrophils from patients with high risk of type I diabetes mellitus in relationto IL-8, IL-10 and IL-12 production and apoptosis in Vitro. Scand J Immunol 2002;55:210-7
  24. Shah SV, Wallin JD, Eilen SD. Chemilnescence and superoxide anion production by leucocytes from diabetic patients. J Clin Endocrinol Metab 1983;57:402-9
  25. Nielson CP, Hindson DA. Inhibition of polymorphonuclear leukocyte respiratory burst by elevated glucose concentrations in vitro. Diabetes 1989;38: 1031-5
  26. Hebert MJ, Takano T, Holthofer H, Brady HR. Sequential morphologic events during apoptosis of human neutrophils. Modulation by lipoxygenasederivedeicosanoids. J Immunol 1996;157:3105-15
  27. Brown SB, Bailey K, Savill J. Actin is cleaved during constitutive apoptosis. Biochem J 1997;323:233-7
  28. Martin SJ. Reuteling sperger CP, McGahon AJ, Ruder JA, van Schie RC, LaFace DM, et al. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med 1995;182:1545-56
  29. Verhoven B, Krahling S, Schlegel RA, Williamson P. Regulation of phosphatidylserine exposure and phagocytosis of apoptotic T lymphocytes. Cell Death Differ 1999;6:262-70
  30. Watson RW, Redmond HP, Wang JH, Condron C, Bouchier-Hayes D. Neutrophils undergo apoptosis following ingestion of Escherichia coli. The Journal ofImmunol 1996;156:3986-92
  31. Victor JT, Barry LF. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 2000;279:L1005-28
  32. Panus PC, Radi R, Chumley PH, Lillurd RH, Freeman BA. Detection of H2O2 release from vascular endothelial cells. Free Radic Biol Med 1993;14:217-23