LOSS OF SYNDECAN-1 ABROGATES THE PULMONARY PROTECTIVE PHENOTYPE INDUCED BY PLASMA AFTER HEMORRHAGIC SHOCK

Syndecan-1 (Sdc1) is considered a biomarker of injury to the endothelial glycocalyx following hemorrhagic shock, with shedding of Sdc1 deleterious. Resuscitation with fresh frozen plasma (FFP) has been correlated with restitution of pulmonary Sdc1 and reduction of lung injury, but the precise contribution ofSdc1 to FFPs protection in the lung remains unclear. Human lungendothelial cellswere used to assess the timeand dose-dependent effect ofFFPonSdc1expression and the effect of Sdc1 silencing on in vitro endothelial cell permeability and actin stress fiber formation. Wild-type and Sdc1(-/-) mice were subjectedtohemorrhagic shock followedby resuscitationwith lactated Ringers (LR) orFFPand comparedwith shock aloneand shams. Lungs were harvested after 3 h for analysis of permeability, histology, and inflammation and for measurement of syndecan-2 and 4 expression. In vitro, FFP enhanced pulmonary endothelial Sdc1 expression in time-and dose-dependent manners and loss of Sdc1 in pulmonary endothelial cellsworsened permeabilityand stress fiber formation by FFP. LossofSdc1 in vivo led to equivalency between LR and FFPin restoring pulmonary injury, inflammation, and permeability after shock. Lastly, Sdc1(-/-) mice demonstrated a significant increase in pulmonary syndecan 4 expression after hemorrhagic shock and FFPbased resuscitation. Taken together, our findings support a key role for Sdc1 in modulating pulmonary protection by FFP after hemorrhagic shock. Our results also suggest that other members of the syndecan family may at least be contributing to FFP's effects on the endothelium, an area that warrants further investigation.