Tissue injury following ischemia-reperfusion (I/R) occurs as a consequence of 
actions of soluble factors and immune cells. Growing evidence supports a role 
for platelets in the manifestation of tissue damage following I/R. Spleen 
tyrosine kinase has been well documented to be important in lymphocyte 
activation and more recently in platelet activation. We performed experiments to 
evaluate whether inhibition of platelet activation through inhibition of spleen 
tyrosine kinase prevents tissue damage after mesenteric I/R injury. Platelets 
isolated from C57BL/6J mice fed with R788 for 10 days were transfused into 
C57BL/6J mice depleted of platelets 2 days before mesenteric I/R injury. 
Platelet-depleted mice transfused with platelets from R788-treated mice before 
mesenteric I/R displayed a significant reduction in the degree of remote lung 
damage, but with little change in the degree of local intestinal damage compared 
with control I/R mice. Transfusion of R788-treated platelets also decreased 
platelet sequestration, C3 deposition, and immunoglobulin deposition in lung, 
but not in the intestine, compared with control groups. These findings 
demonstrate that platelet activation is a requisite for sequestration in the 
pulmonary vasculature to mediate remote tissue injury after mesenteric I/R. The 
use of small-molecule inhibitors may be valuable to prevent tissue damage in 
remote organs following I/R injury.