(258) Histidine-Rich Glycoprotein Ameliorates Lung Ischemia-Reperfusion Injury in a Mouse

Purpose Histidine-rich glycoprotein (HRG) is a multifunctional plasma glycoprotein involved in the regulation of coagulation, fibrinolysis, and inflammation. Recently, decreased plasma levels of HRG at 72 hours after lung transplantation (LT) has been shown to be associated with severe primary graft dysfunction and decreased overall survival after LT. In this study, we investigated the effect of supplementary HRG treatment on lung ischemia-reperfusion injury (IRI) using a mouse hilar clamp model. Methods Mice were divided into the four groups, including the sham-operated group, the IRI group with supplementation of PBS, human serum albumin, or HRG (the HRG group) (n=5 for each group). We assessed lung function, lung injury, pulmonary neutrophil infiltrations, lung cell apoptosis, and inflammatory mediator expression between the groups. Results Compared to the other groups, the HRG group had significantly better PaO2 and significant attenuation of lung injury (Figure). In the HRG group, neutrophil infiltration and prevalence of apoptotis in the reperfused lung was significantly less than the other groups. Moreover, the expression of neutrophil-associated inflammatory mediators in the reperfused lung, including CXCL1, MIP-1α, MIP-1β, G-CSF, GM-CSF, IL-1β, IL-6, and IL-10, were significantly decreased in the HRG group. Conclusion In this study, supplementary HRG treatment suppressed neutrophil-associated inflammatory responses and improved lung IRI in a mouse. HRG may be a potential therapeutic agent for lung IRI.