Abstract
The robust inflammatory response that occurs during ischemia reperfusion (IR) injury recruits factors from both the innate and adaptive immune systems. However the contribution of platelets and their products such as Platelet Factor 4 (PF4; CXCL4), during the pathogenesis of IR injury has not been thoroughly investigated. We show that a deficiency in PF4 protects mice from local and remote tissue damage after 30 minutes of mesenteric ischemia and 3 hours of reperfusion in PF4-/- mice compared to control B6 mice. This protection was independent from Ig or complement deposition in the tissues. However, neutrophil and monocyte infiltration were decreased in the lungs of PF4-/- mice compared with B6 control mice. Platelet-depleted B6 mice transfused with platelets from PF4-/- mice displayed reduced tissue damage compared with controls. In contrast, transfusion of B6 platelets into platelet depleted PF4-/- mice reconstituted damage in both intestine and lung tissues. We also show that PF4 may modulate the release of IgA. Interestingly, we show that PF4 expression on intestinal epithelial cells is increased after IR at both the mRNA and protein levels. In conclusion, these findings demonstrate that may PF4 represent an important mediator of local and remote tissue damage.
Highlights
Ischemia reperfusion (IR) injury is defined as tissue damage occurring after a transient loss of blood supply and subsequent return [1]
To exclude the possibility that Platelet Factor 4 (PF4) protein in the intestine was plateletassociated and to verify that it was produced by intestinal epithelial cells (IEC), we stained for PF4 in intestine and lung tissue sections obtained from platelet depleted mice that were either sham-treated or had undergone mesenteric IR injury (Figure S1B, C)
These findings suggest that intestinal epithelial cells may be a novel source of PF4 and may play a role in tissue damage following mesenteric IR injury
Summary
Ischemia reperfusion (IR) injury is defined as tissue damage occurring after a transient loss of blood supply and subsequent return [1]. During this process an extensive activation of the inflammatory response first locally and to almost all remote organs leading to tissue damage [2]. There is little is known on the role of IgA in tissue damage after IR injury It has been reported, that IgA is a poor activator of complement due to its inability to bind C1q, it can initiate complement activation via the alternate pathway [10]. Natural IgM and mucosal IgA may initiate tissue injury using different but overlapping complement activation pathways
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
