Neutrophil-endothelial cell interactions during the development of tolerance to ischaemia/reperfusion in isolated...

Ischaemia/reperfusion (I/R) tolerance refers to the phenomenon by which the inflammation and associated sequelae induced by I/R is ameliorated by an I/R challenge imposed 24 h earlier. The development of I/R tolerance is dependent on the synthesis of new proteins. In vivo and in vitro studies provide support for nitric oxide synthase (NOS), antioxidant enzymes, and heat shock proteins (HSPs) as the effector proteins. Activation of the nuclear transcription factor, NFkappaB, appears to be a prerequisite for the development of I/R tolerance. In vitro approaches using anoxia/reoxygenation (A/R) to mimic I/R have provided insights into the complexity of the development of I/R tolerance, i.e. different cells may use different signalling pathways to develop A/R tolerance and influence the responses of adjacent cells during the process. The use of cells from genetically altered mice is expediting attempts to unravel specific mechanisms involved in the development of A/R tolerance.