Immunomodulation of hepatic ischemic injury via increased Bcl-XL and decreased Bcl-XS

Kenneth J. Woodside, Juquan Song, Wei Song, Mingdao Hu, Tao Meng, Glenn C. Hunter, Steven Wolf, John A. Daller

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background. Although classic ischemia-reperfusion injury is mediated by reactive oxygen intermediaries, increasing evidence implicates a role for immune-mediated apoptosis during ischemic injury in transplantation. Herein, we report the effects of polyclonal rabbit anti-thymocyte globulin (rATG) on mediators of hepatic apoptosis during cold storage. Methods. Three-month-old male Lewis rats were placed under halothane anesthesia and the portal vein cannulated. University of Wisconsin (UW) solution (35 ml) with (n = 5) and without (n = 5) 20 mg/kg anti-rat rATG was infused before hepatectomy. The liver was stored in UW solution ± rATG (143 ng/ml) at 4°C for various times up to 24 h. Specimens were terminal deoxyuridine nick end labeling-stained for apoptosis. Tissue lysates were analyzed by Western blotting and densitometry. Results. Compared to UW alone, significantly fewer apoptotic cells were present in UW + rATG perfused and stored livers. There were early and sustained significant increases in Bcl-XL and decreases in Bcl-XS with rATG. There was an initial, but not sustained, significant decrease in Bax with rATG. Moreover, there was a significant one-third decrease in caspase-9 production with rATG at 0, 6, 12, and 18 h. Conclusion. Decreased proapoptotic Bcl-XS and increased antiapoptotic Bcl-XL, as well as decreased downstream proapoptotic caspase-9 expression, during liver ischemia after treatment with rATG, all favor cell survival. Because apoptotic ischemic injury results in allograft dysfunction, preservation strategies that ameliorate such immunological effects may improve organ function.

Original languageEnglish (US)
Pages (from-to)59-64
Number of pages6
JournalJournal of Surgical Research
Volume112
Issue number1
DOIs
StatePublished - Jun 1 2003

Fingerprint

Antilymphocyte Serum
Immunomodulation
Rabbits
Liver
Wounds and Injuries
Caspase 9
Apoptosis
Deoxyuridine
Densitometry
Hepatectomy
Halothane
Portal Vein
Reperfusion Injury
Allografts
Cell Survival
Ischemia
Anesthesia
Transplantation
Western Blotting
Oxygen

Keywords

  • Apoptosis
  • Bcl-2
  • Bcl-X
  • Caspase-9
  • Cold storage
  • Immunosuppression
  • Ischemia
  • Liver transplantation
  • Rabbit anti-thymocyte globulin (rATG)
  • University of Wisconsin solution

ASJC Scopus subject areas

  • Surgery

Cite this

Immunomodulation of hepatic ischemic injury via increased Bcl-XL and decreased Bcl-XS . / Woodside, Kenneth J.; Song, Juquan; Song, Wei; Hu, Mingdao; Meng, Tao; Hunter, Glenn C.; Wolf, Steven; Daller, John A.

In: Journal of Surgical Research, Vol. 112, No. 1, 01.06.2003, p. 59-64.

Research output: Contribution to journalArticle

Woodside, Kenneth J. ; Song, Juquan ; Song, Wei ; Hu, Mingdao ; Meng, Tao ; Hunter, Glenn C. ; Wolf, Steven ; Daller, John A. / Immunomodulation of hepatic ischemic injury via increased Bcl-XL and decreased Bcl-XS In: Journal of Surgical Research. 2003 ; Vol. 112, No. 1. pp. 59-64.
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abstract = "Background. Although classic ischemia-reperfusion injury is mediated by reactive oxygen intermediaries, increasing evidence implicates a role for immune-mediated apoptosis during ischemic injury in transplantation. Herein, we report the effects of polyclonal rabbit anti-thymocyte globulin (rATG) on mediators of hepatic apoptosis during cold storage. Methods. Three-month-old male Lewis rats were placed under halothane anesthesia and the portal vein cannulated. University of Wisconsin (UW) solution (35 ml) with (n = 5) and without (n = 5) 20 mg/kg anti-rat rATG was infused before hepatectomy. The liver was stored in UW solution ± rATG (143 ng/ml) at 4°C for various times up to 24 h. Specimens were terminal deoxyuridine nick end labeling-stained for apoptosis. Tissue lysates were analyzed by Western blotting and densitometry. Results. Compared to UW alone, significantly fewer apoptotic cells were present in UW + rATG perfused and stored livers. There were early and sustained significant increases in Bcl-XL and decreases in Bcl-XS with rATG. There was an initial, but not sustained, significant decrease in Bax with rATG. Moreover, there was a significant one-third decrease in caspase-9 production with rATG at 0, 6, 12, and 18 h. Conclusion. Decreased proapoptotic Bcl-XS and increased antiapoptotic Bcl-XL, as well as decreased downstream proapoptotic caspase-9 expression, during liver ischemia after treatment with rATG, all favor cell survival. Because apoptotic ischemic injury results in allograft dysfunction, preservation strategies that ameliorate such immunological effects may improve organ function.",
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AU - Song, Wei

AU - Hu, Mingdao

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AU - Hunter, Glenn C.

AU - Wolf, Steven

AU - Daller, John A.

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N2 - Background. Although classic ischemia-reperfusion injury is mediated by reactive oxygen intermediaries, increasing evidence implicates a role for immune-mediated apoptosis during ischemic injury in transplantation. Herein, we report the effects of polyclonal rabbit anti-thymocyte globulin (rATG) on mediators of hepatic apoptosis during cold storage. Methods. Three-month-old male Lewis rats were placed under halothane anesthesia and the portal vein cannulated. University of Wisconsin (UW) solution (35 ml) with (n = 5) and without (n = 5) 20 mg/kg anti-rat rATG was infused before hepatectomy. The liver was stored in UW solution ± rATG (143 ng/ml) at 4°C for various times up to 24 h. Specimens were terminal deoxyuridine nick end labeling-stained for apoptosis. Tissue lysates were analyzed by Western blotting and densitometry. Results. Compared to UW alone, significantly fewer apoptotic cells were present in UW + rATG perfused and stored livers. There were early and sustained significant increases in Bcl-XL and decreases in Bcl-XS with rATG. There was an initial, but not sustained, significant decrease in Bax with rATG. Moreover, there was a significant one-third decrease in caspase-9 production with rATG at 0, 6, 12, and 18 h. Conclusion. Decreased proapoptotic Bcl-XS and increased antiapoptotic Bcl-XL, as well as decreased downstream proapoptotic caspase-9 expression, during liver ischemia after treatment with rATG, all favor cell survival. Because apoptotic ischemic injury results in allograft dysfunction, preservation strategies that ameliorate such immunological effects may improve organ function.

AB - Background. Although classic ischemia-reperfusion injury is mediated by reactive oxygen intermediaries, increasing evidence implicates a role for immune-mediated apoptosis during ischemic injury in transplantation. Herein, we report the effects of polyclonal rabbit anti-thymocyte globulin (rATG) on mediators of hepatic apoptosis during cold storage. Methods. Three-month-old male Lewis rats were placed under halothane anesthesia and the portal vein cannulated. University of Wisconsin (UW) solution (35 ml) with (n = 5) and without (n = 5) 20 mg/kg anti-rat rATG was infused before hepatectomy. The liver was stored in UW solution ± rATG (143 ng/ml) at 4°C for various times up to 24 h. Specimens were terminal deoxyuridine nick end labeling-stained for apoptosis. Tissue lysates were analyzed by Western blotting and densitometry. Results. Compared to UW alone, significantly fewer apoptotic cells were present in UW + rATG perfused and stored livers. There were early and sustained significant increases in Bcl-XL and decreases in Bcl-XS with rATG. There was an initial, but not sustained, significant decrease in Bax with rATG. Moreover, there was a significant one-third decrease in caspase-9 production with rATG at 0, 6, 12, and 18 h. Conclusion. Decreased proapoptotic Bcl-XS and increased antiapoptotic Bcl-XL, as well as decreased downstream proapoptotic caspase-9 expression, during liver ischemia after treatment with rATG, all favor cell survival. Because apoptotic ischemic injury results in allograft dysfunction, preservation strategies that ameliorate such immunological effects may improve organ function.

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KW - University of Wisconsin solution

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