THE ROLE OF RESIDENT MAST CELLS IN ISCHAEMIA-REPERFUSION INJURY OF SKELETAL MUSCLE.

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/209113

Funding Status
Closed

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Funded Activity Summary

NHMRC 209113 LAY DESCRIPTION Ischaemia reperfusion injury occurs in skeletal muscle when the blood-oxygen supply is cut off (ischaemia) and later restored (reperfusion). If the duration of ischaemia is short some of the muscle survives. However, when blood flow and oxygen are restored the muscle is subjected to more injury, which is thought to be caused by oxygen and-or white blood cells. This type of injury occurs in muscle which has been crushed, limbs that have been broken or traumatized, in replantation of amputated parts, in transplantation, after some surgical procedures and after microsurgical transfer of muscle. Once established there is no effective treatment. Our experiments show that a particular cell, the mast cell, and a particular molecule, nitric oxide, are involved in causing ischaemia reperfusion injury. However, the extent of their involvement is unknown. In this proposal we will investigate the effect of replacing mast cells into muscles, in a unique variety of mice which normally don t contain mast cells and are resistant to ischaemia reperfusion injury. In one group of mice we will put back normal mast cells and in a second group of mice we will put back mast cells that cannot produce the nitric oxide molecule. These experiments will determine, unambiguously, the extent of involvement of mast cells and mast cell-derived nitric oxide. In the second part of this proposal will carry out a time course study, using pharmacologically induced mast cell degranulation, to determine when the mast cells become injurious to skeletal muscle. These experiments will identify the period during which mast cell behaviour can be modulated in order to protect the muscle from ischaemia reperfusion injury. Determination of the role of mast cells, and an understanding of the timing during which they become injurious would provide a logical basis for optimizing drug therapy in clinical applications of these findings.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $226,320.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Surgery

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

ischaemia-reperfusion injury | mast cells | morphology | murine model | reconstructive surgery | skeletal muscle | traumatic injuries

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