Reperfusion injury to tissue following an ischemic event occurs as a consequence 
of an acute inflammatory response that can cause significant morbidity and 
mortality. Components of both the innate (complement, immunoglobulin, monocytes, 
and neutrophils) and adaptive (B and T lymphocytes) immune systems have been 
demonstrated to mediate tissue injury. Spleen tyrosine kinase (Syk) is 
responsible for membrane-mediated signaling in various cell types including B 
lymphocytes, macrophages, and T cells. We investigated the ability of a small 
drug Syk inhibitor, R788, to protect mice against mesenteric 
ischemia-reperfusion (I/R)-induced local (intestine) and remote lung injury. 
Mice were fed with chow containing a Syk inhibitor for 6 days before the 
performance of intestinal I/R, which resulted in silencing of the expression of 
the active phosphorylated Syk. Syk inhibition significantly suppressed both 
local and remote lung injury. The beneficial effect was associated with reduced 
IgM and complement 3 deposition in the tissues and significant reduction of 
polymorphonuclear cell infiltration. Our data place Syk upstream of events 
leading to the binding of natural antibodies to the ischemia-conditioned tissues 
and urge the consideration of the use of Syk inhibitors in the prevention or 
improvement of tissue injury of organs exposed to ischemia or hypoperfusion.