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Granülosit-makrofaj koloni-stimülan factor uygulanması bozulmuş flep iyileşmesinde doku CD4/CD8 oranını arttırıyormu?

Yıl 2009, Cilt: 6 Sayı: 1, 11 - 17, 01.04.2009

Öz

Amaç: Yara iyileşmesinde T hücre bağımlı immün yanıtın sağlıklı olması esansiyel öneme sahiptir. Glukokortikoidler T hücre proliferasyonunu inhibe ederek hücresel yanıtı bozmalarına karşın bir proinflamatuar sitokin olan granülositmakrofaj koloni stimülan faktör GM-CSF dolaşımdaki CD4/CD8 oranını arttırarak immün stimülasyon gerçekleşir. Bu çalışmada bozulmuş yara iyileşmesi modelinde lenfositlerin rolünün immunhistokimyasal olarak ortaya konulması amaçlanmıştır. Gereç - Yöntem: 72 adet Wistar albino rat 200 – 240 g arası üç gruba ayrılmıştır: I Grup Serum fizyolojik + flep kaldırma ; II Grup Sistemik metilprednizolon uygulaması + serum fizyolojik + flep kaldırma ; III Grup Sistemik metilprednizolon uygulaması + GM-CSF + serum fizyolojik + flep kaldırma . Doku örenkleri % 10’ luk formalinde fikse fiksasyonun ardından parafine gömüldükten sonra kullanılmıştır. Örneklerden alınan kesitler CD4 ve CD8 monoklonal antikorları ile boyandıktan sonra immünohistokimyasal olarak incelenmiştir. Bulgular: I Gruptaki kesitlerden daha kötü olmasına karşılık CD4 ve CD8 ile boyanma III Gruba ait histolojik kesitlerde II Gruba ait olanlardan daha iyi boyanmıştır P

Kaynakça

  • Smith PD, Kuhn MA, Franz MG, et al. Initiating the inflammatory phase of incisional healing prior to tissue injury. J Surg Res, 2000; 92:11-7.
  • Robson MC, Dubay DA, Wang X, Franz MG.
  • Effect of cytokine growth factors on the prevention of acute wound failure. Wound Repair Regen, 2004; 12:38-3.
  • Carrico TJ, Mehrhof AI, Cohen IK. Biology of wound healing. Surg Clin North Am, 1984; 64:721-733.
  • Sporn MB, Roberts AB. Peptide growth factors and inflammation, tissue repair, and cancer. J Clin Invest, 1986; 78:329-2.
  • Chircop MP, Yu Y, Berney CR, et al. Wound healing and growth factor expression in T lymphocyte deficiency. ANZ J Surg, 2002; 72: 491-5.
  • Mast BA, Schultz GS. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair Regen, 1996; 4:411-20.
  • Greenhalgh DG. The role of growth factors in wound healing. J Trauma, 1996; 41:159-67.
  • Jyung RW, Wu L, Pierce GF, Mustoe TA. Granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor: differential action on incisional wound healing. Surgery, 1994; 115:325-34.
  • Fang Y, Gong SJ, Xu YH, Hambly BD, Bao S. Impaired cutaneous wound healing in granulocyte/macrophage colony-stimulating factor knockout mice. Br J Dermatol, 2007; 157:458-65.
  • Marques da Costa R, Jesus FM, Aniceto C, Mendes M. placebo-controlled trial of the use of granulocyte-macrophage colony-stimulating factor in chronic leg ulcers. Am J Surg, 1997; 173:165-8. randomized
  • Gawronska-Kozak B, Bogacki M, Rim JS, Monroe WT, Manuel JA. Scarless skin repair in immunodeficient mice. Wound Repair Regen, 2006; 14: 265-76.
  • Boyce DE, Jones WD, Ruge F, Harding KG, Moore K. The role of lymphocytes in human dermal wound healing. Br J Dermatol, 2000; 143:59-65.
  • Dal Pra I, Freddi G, Minic J, Chiarini A, Armato U. De novo engineering of reticular connective tissue in vivo by silk fibroin nonwoven materials. Biomaterials, 2005; 26: 1987-1999.
  • Barbul A. Immune aspects of wound repair. Clin Plast Surg, 1990; 17:433-42.
  • Baum CL, Arpey CJ. Normal cutaneous wound healing: clinical correlation with cellular and molecular events. Dermatol Surg, 2005; 31:674-86.
  • Ergun SS, Kiran B, Su O, et al. Effects of granulocyte macrophage colony stimulating factor on random flap healing and immune profile in rats with impaired wound healing by glucocorticoids. Ann Plast Surg, 2004; 52:80- 8.
  • Park JE, Barbul A. Understanding the role of immune regulation in wound healing. Am J Surg, 2004; 187:11S-16S.
  • Conway K, Ruge F, Price P, Harding KG, Jiang WG. Hepatocyte growth factor regulation: an integral part of why wounds become chronic. Wound Repair Regen, 2007; 15:683-92.
  • Davis PA, Corless DJ, Aspinall R, Wastell C. Effect of CD4(+) and CD8(+) cell depletion on wound healing. Br J Surg, 2001; 88:298- 304.
  • Barbul A, Regan MC. Immune involvement in wound healing. Otolaryngol Clin North Am 1995; 28:955-68.
  • Breslin RJ, Wasserkrug HL, Efron G, Barbul A. Suppressor cell generation during normal wound healing. J Surg Res, 1988; 44:321-25.
  • Flohé S, Flohé SB, Schade FU, Waydhas C. Immune response of severely injured patients - influence of surgical intervention and therapeutic impact. Langenbecks Arch Surg, 2007; 392:639-48.
  • Peterson JM, Barbul A, Breslin RJ, Wasserkrug HL, Efron G. Significance of T- lymphocytes in wound healing. Surgery, 1987; 102:300-305.
  • Wahl SM. Glucocorticoids and wound healing. In: Schleimer RP, Claman HN, Oronsky A, eds. Anti-Inflammatory Steroid Action: Basic and Clinical Aspects, New York: Academic Press, 1989; 280–302.
  • Tarr PE. Granulocyte-macrophage colony- stimulating factor and the immune system. Med Oncol, 1996; 13:133-40.
  • Schäffer M, Barbul A. Lymphocyte function in wound healing and following injury. Br J Surg 1998; 85: 444-60.
  • Barbul A, Breslin RJ, Woodyard JP, Wasserkrug HL, Efron G. The effect of in vivo T helper and T suppressor lymphocyte depletion on wound healing. Ann Surg, 1989; 209:479-83.
  • Reinherz EL, Schlossman SF. The differentiation and function of human T lymphocytes. Cell, 1980; 19:821-27.
  • Chess L. The birth of functionally distinct T cell subsets. J Immunol, 2006; 176: 3859-60.
  • Royer HD, Reinherz EL. T lymphocytes: ontogeny, function, and relevance to clinical disorders. N Engl J Med, 1987; 317:1136-42.
  • Mels AK, Statius Muller MG, van Leeuwen PA, et al.Immune-stimulating effects of low- dose perioperative recombinant granulocyte- macrophage colony-stimulating factor in patients operated on for primary colorectal carcinoma. Br J Surg, 2001; 88:539-44.
  • Lim TK, Chen GH, McDonald RA, Toews GB. stimulating immunosuppressive corticosteroids on rat pulmonary dendritic cells. Stem Cells, 1996; 14:292-99.
  • Mann A, Breuhahn K, Schirmacher P, Blessing granulocyte-macrophage colony stimulating factor accelerates wound healing: Stimulation of keratinocyte proliferation, granulation tissue formation, and vascularization. J Invest Dermatol, 2001; 117:1382-90.
  • Mann A, Niekisch K, Schirmacher P, Blessing M. stimulating factor is essential for normal wound healing. J Investig Dermatol Symp Proc, 2006; 11:87-92. colony- factor overrides function of M.
  • Keratinocyte-derived Granulocyte-macrophage colony
  • Robson M, Kucukcelebi A, Carp SS, et al. Effects of granulocyte-macrophage colony- stimulating factor on wound contraction. Eur J Clin Microbiol Infect Dis, 1994; 13:S41-46.
  • El Saghir NS, Bizri AR, Shabb NS, et al. Pressure ulcer accelerated healing with local injections of granulocyte macrophage-colony stimulating factor. J Infect, 1997; 35:179-82.

Does priming granulocyte-macrophage colony-stimulating factor increase tissue CD4/CD8 ratioin impaired flap healing?

Yıl 2009, Cilt: 6 Sayı: 1, 11 - 17, 01.04.2009

Öz

ABSTRACT Background: The presence of an intact T-cell immune system is essential for a normal wound healing. Glucocorticoids impair cellular immune response by inhibiting T-cell proliferation, but granulocytemacrophage colony-stimulating factor GM-CSF which is a proinflammatory cytokine leads to immune stimulation by increasing the levels of circulating CD4 and CD8 cells. The purpose of this study was to elucidate the role of lymphocytes in impaired wound healing model by using immunohistochemistry. Methods: 72 Wistar albino rats 200 to 240 g were divided into three groups: Group I given saline + flap elevation ; Group II given systemic methylprednisolone + saline + flap elevation ; Group III given systemic methylprednisolone + GM-CSF + flap elevation . Samples fixed in 10 % formaline and embedded in parafin were used. The sample sections were evaluated immunohistochemically using monoclonal antibodies for CD4 and CD8. Results: CD4 and CD8 staining of histologic sections in GM-CSF-treated group III were better than those of group II, although they all remained worst than those of group I p> 0.05 . Conclusions: The results obtained in this study, suggest the possiblity to abrogate the immunesuppressive effects of methylprednisolone by GM-CSF injection. To restore lymphocyte function using proinflammatory cytokines is important for wound healing and prevention of immunosuppression

Kaynakça

  • Smith PD, Kuhn MA, Franz MG, et al. Initiating the inflammatory phase of incisional healing prior to tissue injury. J Surg Res, 2000; 92:11-7.
  • Robson MC, Dubay DA, Wang X, Franz MG.
  • Effect of cytokine growth factors on the prevention of acute wound failure. Wound Repair Regen, 2004; 12:38-3.
  • Carrico TJ, Mehrhof AI, Cohen IK. Biology of wound healing. Surg Clin North Am, 1984; 64:721-733.
  • Sporn MB, Roberts AB. Peptide growth factors and inflammation, tissue repair, and cancer. J Clin Invest, 1986; 78:329-2.
  • Chircop MP, Yu Y, Berney CR, et al. Wound healing and growth factor expression in T lymphocyte deficiency. ANZ J Surg, 2002; 72: 491-5.
  • Mast BA, Schultz GS. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair Regen, 1996; 4:411-20.
  • Greenhalgh DG. The role of growth factors in wound healing. J Trauma, 1996; 41:159-67.
  • Jyung RW, Wu L, Pierce GF, Mustoe TA. Granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor: differential action on incisional wound healing. Surgery, 1994; 115:325-34.
  • Fang Y, Gong SJ, Xu YH, Hambly BD, Bao S. Impaired cutaneous wound healing in granulocyte/macrophage colony-stimulating factor knockout mice. Br J Dermatol, 2007; 157:458-65.
  • Marques da Costa R, Jesus FM, Aniceto C, Mendes M. placebo-controlled trial of the use of granulocyte-macrophage colony-stimulating factor in chronic leg ulcers. Am J Surg, 1997; 173:165-8. randomized
  • Gawronska-Kozak B, Bogacki M, Rim JS, Monroe WT, Manuel JA. Scarless skin repair in immunodeficient mice. Wound Repair Regen, 2006; 14: 265-76.
  • Boyce DE, Jones WD, Ruge F, Harding KG, Moore K. The role of lymphocytes in human dermal wound healing. Br J Dermatol, 2000; 143:59-65.
  • Dal Pra I, Freddi G, Minic J, Chiarini A, Armato U. De novo engineering of reticular connective tissue in vivo by silk fibroin nonwoven materials. Biomaterials, 2005; 26: 1987-1999.
  • Barbul A. Immune aspects of wound repair. Clin Plast Surg, 1990; 17:433-42.
  • Baum CL, Arpey CJ. Normal cutaneous wound healing: clinical correlation with cellular and molecular events. Dermatol Surg, 2005; 31:674-86.
  • Ergun SS, Kiran B, Su O, et al. Effects of granulocyte macrophage colony stimulating factor on random flap healing and immune profile in rats with impaired wound healing by glucocorticoids. Ann Plast Surg, 2004; 52:80- 8.
  • Park JE, Barbul A. Understanding the role of immune regulation in wound healing. Am J Surg, 2004; 187:11S-16S.
  • Conway K, Ruge F, Price P, Harding KG, Jiang WG. Hepatocyte growth factor regulation: an integral part of why wounds become chronic. Wound Repair Regen, 2007; 15:683-92.
  • Davis PA, Corless DJ, Aspinall R, Wastell C. Effect of CD4(+) and CD8(+) cell depletion on wound healing. Br J Surg, 2001; 88:298- 304.
  • Barbul A, Regan MC. Immune involvement in wound healing. Otolaryngol Clin North Am 1995; 28:955-68.
  • Breslin RJ, Wasserkrug HL, Efron G, Barbul A. Suppressor cell generation during normal wound healing. J Surg Res, 1988; 44:321-25.
  • Flohé S, Flohé SB, Schade FU, Waydhas C. Immune response of severely injured patients - influence of surgical intervention and therapeutic impact. Langenbecks Arch Surg, 2007; 392:639-48.
  • Peterson JM, Barbul A, Breslin RJ, Wasserkrug HL, Efron G. Significance of T- lymphocytes in wound healing. Surgery, 1987; 102:300-305.
  • Wahl SM. Glucocorticoids and wound healing. In: Schleimer RP, Claman HN, Oronsky A, eds. Anti-Inflammatory Steroid Action: Basic and Clinical Aspects, New York: Academic Press, 1989; 280–302.
  • Tarr PE. Granulocyte-macrophage colony- stimulating factor and the immune system. Med Oncol, 1996; 13:133-40.
  • Schäffer M, Barbul A. Lymphocyte function in wound healing and following injury. Br J Surg 1998; 85: 444-60.
  • Barbul A, Breslin RJ, Woodyard JP, Wasserkrug HL, Efron G. The effect of in vivo T helper and T suppressor lymphocyte depletion on wound healing. Ann Surg, 1989; 209:479-83.
  • Reinherz EL, Schlossman SF. The differentiation and function of human T lymphocytes. Cell, 1980; 19:821-27.
  • Chess L. The birth of functionally distinct T cell subsets. J Immunol, 2006; 176: 3859-60.
  • Royer HD, Reinherz EL. T lymphocytes: ontogeny, function, and relevance to clinical disorders. N Engl J Med, 1987; 317:1136-42.
  • Mels AK, Statius Muller MG, van Leeuwen PA, et al.Immune-stimulating effects of low- dose perioperative recombinant granulocyte- macrophage colony-stimulating factor in patients operated on for primary colorectal carcinoma. Br J Surg, 2001; 88:539-44.
  • Lim TK, Chen GH, McDonald RA, Toews GB. stimulating immunosuppressive corticosteroids on rat pulmonary dendritic cells. Stem Cells, 1996; 14:292-99.
  • Mann A, Breuhahn K, Schirmacher P, Blessing granulocyte-macrophage colony stimulating factor accelerates wound healing: Stimulation of keratinocyte proliferation, granulation tissue formation, and vascularization. J Invest Dermatol, 2001; 117:1382-90.
  • Mann A, Niekisch K, Schirmacher P, Blessing M. stimulating factor is essential for normal wound healing. J Investig Dermatol Symp Proc, 2006; 11:87-92. colony- factor overrides function of M.
  • Keratinocyte-derived Granulocyte-macrophage colony
  • Robson M, Kucukcelebi A, Carp SS, et al. Effects of granulocyte-macrophage colony- stimulating factor on wound contraction. Eur J Clin Microbiol Infect Dis, 1994; 13:S41-46.
  • El Saghir NS, Bizri AR, Shabb NS, et al. Pressure ulcer accelerated healing with local injections of granulocyte macrophage-colony stimulating factor. J Infect, 1997; 35:179-82.
Toplam 38 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Araştırma Makalesi
Yazarlar

İbrahim Ethem Ulagay Bu kişi benim

Yayımlanma Tarihi 1 Nisan 2009
Yayımlandığı Sayı Yıl 2009 Cilt: 6 Sayı: 1

Kaynak Göster

Vancouver Ulagay İE. Granülosit-makrofaj koloni-stimülan factor uygulanması bozulmuş flep iyileşmesinde doku CD4/CD8 oranını arttırıyormu?. Harran Üniversitesi Tıp Fakültesi Dergisi. 2009;6(1):11-7.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty