Hepatic ischemia-reperfusion injury (IRI) remains an important clinical problem.[16, 17] In transplantation, its significance is enhanced by the increased use of extended criteria donor organs. Oxygen deprivation induces death of hepatocytes,

which release various DAMPs, such as high-mobility group box B1 (HMGB-1), self-DNA, Selinexor solubility dmso self-SNA, and ATP. DAMPs stimulate innate immune mechanisms through cell-associated pattern recognition receptors, which include Toll-like receptors (TLRs), HMGB-1-like receptors, C-type lectin receptors, and nucleotide-binding domain leucine-rich repeats,[18] expressed on innate immune cells. Triggering of DCs by these receptors induces their activation and maturation.[19] DCs have been implicated in the regulation of inflammation and tissue

injury after liver IR,[4, 20-22] with both inhibitory and enhancing effects being reported. Though there is evidence for a protective role of CD39 in total hepatic warm ischemia[23] and liver cold IRI[24] based on studies using CD39−/− mice and CD39-overexpressing mice, respectively, Tyrosine Kinase Inhibitor Library in vitro cold IRI is more clinically relevant for assessing tissue injury during liver transplantation (LT). Here, we examined the expression and function of CD39 on liver conventional myeloid DCs (mDCs) in vitro and using a cold liver IRI model in vivo. Our novel findings suggest that expression of CD39 on liver mDCs attenuates their proinflammatory activity and exerts a protective affect against Fossariinae extended cold liver

preservation injury. Male C57BL/6 (B6;H-2b) and BALB/c (H-2d) mice (8 to 12 weeks old) were purchased from The Jackson Laboratory (Bar Harbor, ME). CD39−/− mice (B6 background) were bred from pairs received from the Beth Israel Medical Center, Harvard University (Boston, MA). Animals were maintained in the specific pathogen-free Central Animal Facility of the University of Pittsburgh School of Medicine (Pittsburgh, PA). Experiments were conducted under an institutional animal care and use committee–approved protocol and in accord with criteria outlined in the National Institutes of Health publication, Guide for the Care and Use of Laboratory Animals. Mice were fed a diet of Purina rodent chow (Ralston Purina, St. Louis, MO) and received tap water ad libitum. ATP was purchased from Sigma-Aldrich (St. Louis, MO) and Escherichia coli lipopolysaccharide (LPS) was from InvivoGen (San Diego, CA). DCs were isolated and purified as previously described.[7, 25] Thus, livers, kidneys, and spleens were harvested from mice given recombinant human fms-like tyrosine kinase 3 ligand (10 μg/day intraperitoneally for 10 days; Amgen Inc., Seattle, WA) and digested in collagenase (Sigma-Aldrich).