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A P-selectin-immunoglobulin G chimera is protective in a rabbit ear model of ischemia-reperfusion
W P Lee1, P Gribling, L De Guzman
1Department of Endocrinology, Genetech, South San Francisco, CA 94080, USA.
Background:
Neutrophils have been shown to play a role in ischemia-reperfusion injury, and the initial interaction of neutrophils with the endothelium is mediated through the selectin family of adhesion molecules. Thus the purpose of these studies was to determine whether a P-selectin-IgG chimera was protective in a model of ischemia-reperfusion injury.
Methods:
The model used was a rabbit ear model of ischemia-reperfusion. Selectin-IgG chimeras were given at the time of reperfusion of the tissue, and their efficacy was compared with an anti-CD18 antibody (MHM23).
Results:
The P-selectin-IgG was as protective in this model as an anti-CD18 antibody. The chimera did not mediate its effect by causing the animals to become neutropenic.
Conclusions:
P-selectin plays a role in ischemia-reperfusion injury. This is in agreement with data from other groups. The fact that the chimera was effective in this model suggests that carbohydrates or small molecule mimics of carbohydrates would be effective in this model. Such antiinflammatory agents may have fewer side effects in terms of increased risk of sepsis.