The induction of ICAM-1 and Mn SOD in response to ischemia-reperfusion of skeletal muscle in humans

Research output: Contribution to journalArticle

Abstract

Introduction: Ischemia-reperfusion results in the release of cytokine mediators of inflammation due to tissue damage. Different cytokines, e.g. TNFα, IL-1β, and chemokines induce expression of intercellular adhesion molecule-1 (ICAM-1) which in turn binds to the integrins (LFA-1, Mac-1) of leukocytes. Reperfusion injury is also caused by superoxides generated by activated neutrophils. In order to attenuate superoxide-induced tissue damage, the mitochondrial superoxide scavanging enzyme, manganese-superoxide dismutase (MnSOD), is produced during oxidative stress of reperfusion. In this study, we examined the levels of induction of ICAM-1, several cytokines and MnSOD activity to evaluate reperfusion injury in humans subjected to tourniquet induced lower extremity ischemia. Methods: Muscle biopsies from four patients were collected 5 minutes prior to tourniquet application and 5 minutes after reperfusion. Venous- and arterial blood samples were also collected 5 minutes prior to and 5-, 60-, and 240-minutes after tourniquet release. Differences in the pool level of ICAM-1, TNFα, IL-1β, TGFβ, and MnSOD mRNAs were determined by Northern analysis both in pre- and post-reperfused muscle and blood cells (granulocytes and mononuclear cells). The levels of soluble ICAM-1 in circulatory plasma were also determined. Results: A 2-7 fold increase in ICAM-1 mRNA levels was detected in muscle biopsies 5 minutes after reperfusion, i.e., either in endothelial cells and/or muscle cells at the sites of injury. No changes in the constitutive level of ICAM-1 mRNA levels were observed in blood cells or in sICAM-1 in plasma from the same patient. TNFα and IL-1β were not detected by Northern analysis of the muscle samples. Although the constitutive levels of MnSOD mRNA did not change in either muscle or blood sampled at 5 minutes after reperfusion, a dramatic increase of mRNA level occurred in blood (granulocytes) collected at 60- and 240-minutes after reperfusion. Conclusions: In conclusion, we propose that the induction of ICAM-1 and MnSOD are tissue-specific responses, i.e., skeletal muscle and granulocytes, to ischemia-reperfusion. The high levels of ICAM-1 mRNA in muscle tissues at 5 minutes is an early response and increased MnSOD produced by granulocytes is a late response to attenuate superoxide induced injury following reperfusion.

Original languageEnglish (US)
JournalCritical Care Medicine
Volume27
Issue number1 SUPPL.
StatePublished - 1999

Fingerprint

Intercellular Adhesion Molecule-1
Superoxide Dismutase
Reperfusion
Skeletal Muscle
Ischemia
Granulocytes
Superoxides
Tourniquets
Messenger RNA
Muscles
Reperfusion Injury
Interleukin-1
Cytokines
Muscle Cells
Blood Cells
Biopsy
Inflammation Mediators
Lymphocyte Function-Associated Antigen-1
Chemokines
varespladib methyl

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

The induction of ICAM-1 and Mn SOD in response to ischemia-reperfusion of skeletal muscle in humans. / Huda, R.; Mathru, M.; Prough, Donald; Papaconstantinou, John.

In: Critical Care Medicine, Vol. 27, No. 1 SUPPL., 1999.

Research output: Contribution to journalArticle

@article{7eaa85b545604aec8d67ff4ff182fb2a,
title = "The induction of ICAM-1 and Mn SOD in response to ischemia-reperfusion of skeletal muscle in humans",
abstract = "Introduction: Ischemia-reperfusion results in the release of cytokine mediators of inflammation due to tissue damage. Different cytokines, e.g. TNFα, IL-1β, and chemokines induce expression of intercellular adhesion molecule-1 (ICAM-1) which in turn binds to the integrins (LFA-1, Mac-1) of leukocytes. Reperfusion injury is also caused by superoxides generated by activated neutrophils. In order to attenuate superoxide-induced tissue damage, the mitochondrial superoxide scavanging enzyme, manganese-superoxide dismutase (MnSOD), is produced during oxidative stress of reperfusion. In this study, we examined the levels of induction of ICAM-1, several cytokines and MnSOD activity to evaluate reperfusion injury in humans subjected to tourniquet induced lower extremity ischemia. Methods: Muscle biopsies from four patients were collected 5 minutes prior to tourniquet application and 5 minutes after reperfusion. Venous- and arterial blood samples were also collected 5 minutes prior to and 5-, 60-, and 240-minutes after tourniquet release. Differences in the pool level of ICAM-1, TNFα, IL-1β, TGFβ, and MnSOD mRNAs were determined by Northern analysis both in pre- and post-reperfused muscle and blood cells (granulocytes and mononuclear cells). The levels of soluble ICAM-1 in circulatory plasma were also determined. Results: A 2-7 fold increase in ICAM-1 mRNA levels was detected in muscle biopsies 5 minutes after reperfusion, i.e., either in endothelial cells and/or muscle cells at the sites of injury. No changes in the constitutive level of ICAM-1 mRNA levels were observed in blood cells or in sICAM-1 in plasma from the same patient. TNFα and IL-1β were not detected by Northern analysis of the muscle samples. Although the constitutive levels of MnSOD mRNA did not change in either muscle or blood sampled at 5 minutes after reperfusion, a dramatic increase of mRNA level occurred in blood (granulocytes) collected at 60- and 240-minutes after reperfusion. Conclusions: In conclusion, we propose that the induction of ICAM-1 and MnSOD are tissue-specific responses, i.e., skeletal muscle and granulocytes, to ischemia-reperfusion. The high levels of ICAM-1 mRNA in muscle tissues at 5 minutes is an early response and increased MnSOD produced by granulocytes is a late response to attenuate superoxide induced injury following reperfusion.",
author = "R. Huda and M. Mathru and Donald Prough and John Papaconstantinou",
year = "1999",
language = "English (US)",
volume = "27",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "1 SUPPL.",

}

TY - JOUR

T1 - The induction of ICAM-1 and Mn SOD in response to ischemia-reperfusion of skeletal muscle in humans

AU - Huda, R.

AU - Mathru, M.

AU - Prough, Donald

AU - Papaconstantinou, John

PY - 1999

Y1 - 1999

N2 - Introduction: Ischemia-reperfusion results in the release of cytokine mediators of inflammation due to tissue damage. Different cytokines, e.g. TNFα, IL-1β, and chemokines induce expression of intercellular adhesion molecule-1 (ICAM-1) which in turn binds to the integrins (LFA-1, Mac-1) of leukocytes. Reperfusion injury is also caused by superoxides generated by activated neutrophils. In order to attenuate superoxide-induced tissue damage, the mitochondrial superoxide scavanging enzyme, manganese-superoxide dismutase (MnSOD), is produced during oxidative stress of reperfusion. In this study, we examined the levels of induction of ICAM-1, several cytokines and MnSOD activity to evaluate reperfusion injury in humans subjected to tourniquet induced lower extremity ischemia. Methods: Muscle biopsies from four patients were collected 5 minutes prior to tourniquet application and 5 minutes after reperfusion. Venous- and arterial blood samples were also collected 5 minutes prior to and 5-, 60-, and 240-minutes after tourniquet release. Differences in the pool level of ICAM-1, TNFα, IL-1β, TGFβ, and MnSOD mRNAs were determined by Northern analysis both in pre- and post-reperfused muscle and blood cells (granulocytes and mononuclear cells). The levels of soluble ICAM-1 in circulatory plasma were also determined. Results: A 2-7 fold increase in ICAM-1 mRNA levels was detected in muscle biopsies 5 minutes after reperfusion, i.e., either in endothelial cells and/or muscle cells at the sites of injury. No changes in the constitutive level of ICAM-1 mRNA levels were observed in blood cells or in sICAM-1 in plasma from the same patient. TNFα and IL-1β were not detected by Northern analysis of the muscle samples. Although the constitutive levels of MnSOD mRNA did not change in either muscle or blood sampled at 5 minutes after reperfusion, a dramatic increase of mRNA level occurred in blood (granulocytes) collected at 60- and 240-minutes after reperfusion. Conclusions: In conclusion, we propose that the induction of ICAM-1 and MnSOD are tissue-specific responses, i.e., skeletal muscle and granulocytes, to ischemia-reperfusion. The high levels of ICAM-1 mRNA in muscle tissues at 5 minutes is an early response and increased MnSOD produced by granulocytes is a late response to attenuate superoxide induced injury following reperfusion.

AB - Introduction: Ischemia-reperfusion results in the release of cytokine mediators of inflammation due to tissue damage. Different cytokines, e.g. TNFα, IL-1β, and chemokines induce expression of intercellular adhesion molecule-1 (ICAM-1) which in turn binds to the integrins (LFA-1, Mac-1) of leukocytes. Reperfusion injury is also caused by superoxides generated by activated neutrophils. In order to attenuate superoxide-induced tissue damage, the mitochondrial superoxide scavanging enzyme, manganese-superoxide dismutase (MnSOD), is produced during oxidative stress of reperfusion. In this study, we examined the levels of induction of ICAM-1, several cytokines and MnSOD activity to evaluate reperfusion injury in humans subjected to tourniquet induced lower extremity ischemia. Methods: Muscle biopsies from four patients were collected 5 minutes prior to tourniquet application and 5 minutes after reperfusion. Venous- and arterial blood samples were also collected 5 minutes prior to and 5-, 60-, and 240-minutes after tourniquet release. Differences in the pool level of ICAM-1, TNFα, IL-1β, TGFβ, and MnSOD mRNAs were determined by Northern analysis both in pre- and post-reperfused muscle and blood cells (granulocytes and mononuclear cells). The levels of soluble ICAM-1 in circulatory plasma were also determined. Results: A 2-7 fold increase in ICAM-1 mRNA levels was detected in muscle biopsies 5 minutes after reperfusion, i.e., either in endothelial cells and/or muscle cells at the sites of injury. No changes in the constitutive level of ICAM-1 mRNA levels were observed in blood cells or in sICAM-1 in plasma from the same patient. TNFα and IL-1β were not detected by Northern analysis of the muscle samples. Although the constitutive levels of MnSOD mRNA did not change in either muscle or blood sampled at 5 minutes after reperfusion, a dramatic increase of mRNA level occurred in blood (granulocytes) collected at 60- and 240-minutes after reperfusion. Conclusions: In conclusion, we propose that the induction of ICAM-1 and MnSOD are tissue-specific responses, i.e., skeletal muscle and granulocytes, to ischemia-reperfusion. The high levels of ICAM-1 mRNA in muscle tissues at 5 minutes is an early response and increased MnSOD produced by granulocytes is a late response to attenuate superoxide induced injury following reperfusion.

UR - http://www.scopus.com/inward/record.url?scp=33750801894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750801894&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33750801894

VL - 27

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 1 SUPPL.

ER -