Abstract
We previously reported that ultraviolet light B (UVB)-treated human platelets (hPLTs) can cause acute lung injury (ALI) in a two-event SCID mouse model in which the predisposing event was Lipopolysaccharide (LPS) injection and the second event was infusion of UVB-treated hPLTs. To delineate contributions of host mouse platelets (mPLTs) and neutrophils in the pathogenesis of ALI in this mouse model, we depleted mPLTs or neutrophils and measured hPLT accumulation in the lung. We also assessed lung injury by protein content in bronchoalveolar lavage fluid (BALF). LPS injection followed by infusion of UVB-treated hPLTs resulted in sequestration of both mPLTs and hPLTs in the lungs of SCID mice, although the numbers of neutrophils in the lung were not significantly different from the control group. Depletion of mouse neutrophils caused only a mild reduction in UVB-hPLTs accumulation in the lungs and a mild reduction in protein content in BALF. In comparison, depletion of mPLTs almost completely abolished hPLTs accumulation in the lung and significantly reduced protein content in BALF. UVB-treated hPLTs bound to host mPLTs, but did not bind to neutrophils in the lung. Aspirin treatment of hPLTs in vitro abolished hPLT accumulation in the lung and protected mice from lung injury. Our data indicate that host mPLTs accumulated in the lungs in response to an inflammatory challenge and subsequently mediated the attachment of transfused UVB-hPLTs. Neutrophils also recruited a small percentage of platelets to the lung. These findings may help develop therapeutic strategies for ALI which could potentially result from transfusion of UV illuminated platelets.
Highlights
Platelets are transfused for their life-saving hemostatic benefits, they can be associated with substantial adverse events, such as sepsis, alloimmunization and transfusion-related acute lung injury (TRALI) [1]
We tested whether P-selectin was the molecule that mediated the sequestration of ultraviolet light B (UVB) exposed platelets in the lung. human platelets (hPLTs) were treated with 4 mM of Thrombin receptor-activating peptide (TRAP), which resulted in P-selectin expression on approximately 50% of platelets
Using our previously decribed SCID mouse model of ALI, we further dissected the role of the host mouse platelets (mPLTs) and infused hPLTs, and provided the first evidence for a contribution of host platelets in the development of ALI through recruitment of infused hPLTs
Summary
Platelets are transfused for their life-saving hemostatic benefits, they can be associated with substantial adverse events, such as sepsis, alloimmunization and transfusion-related acute lung injury (TRALI) [1]. Recent animal studies have supported a two-event model [3,4,5,6] in which TRALI requires an immune priming event, most often inflammation, that causes priming of polymorphonuclear cells (PMNs) and activation of pulmonary endothelial cells. This is followed by a transfusion event that introduces biologically active mediators such as lipids and cytokines from stored blood products [5,6,7] or antiHLA antibodies, or anti-granulocyte antibodies [3,4,7]. These biologically active mediators are able to activate the primed PMNs, resulting in pulmonary endothelial cell damage and a capillary leak which are the hallmarks of acute lung injury (ALI) [8]
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