Defective migration of dendritic cell subsets in PI3K deficient mice

Aim. Chemokines play cl ey role in dir eting [eucocyte trafficking by inrerneting with seven-trnnsmembr:mt: domain G-proteincoupled receptor Ch 'mokines and their ree ptor are prime targets for thc dcvelopmt:Ol of new therapeurie strategies aimed at eunrralling <liverst: pathologies. [t is well accepted that CLtI pbys a key role in post-ischemia rt:perfusion injury. Reperta. in is a no e! and sele tiw ·mall organi inhibitor of • CL8 ineluced chemotaxis. Repertaxin dOl:s nor affe t the binding of radiolabel d CXCLS to human PM whereas it inhibits • CLS receptor signaI transcluction e.g CaZ+ mohilization an tyrosine kinase activatjon). Methods. Liver pOst-ischt:mic damage was reprodu ed in mal Wistar rats through a lobar selective in-f1ow occlusion mode/. Nc:crosis was eY:.lluated by ALT and AST levels in pbsma samples and the activity of myeloperoxidase in hepmic samples was used a· an ind x of PM inftitIlIti n, R ults. As 'xpected transient lob:1r selective i.>che· mia (60 min) follm ed by reperfusion (6,12,24 h) induced PMI infiltr:: ltion, a' well as hepatoeellulaI necrosis in the vehicle treatecl animai .. Treatment of rat with Repertaxin Cfour c10ses of 1-mg/kg, cadI one) reclu<.:ed PiVU\, infiltIation by almost 50'% and hepatic irr versibk clamage by 70% after re-flow, as compared to vehicle lreatd animals. Conclusion. 'l'he efficacy in the experimental mode! of li er necrosis inducecl by ischemja/reperfusion along with t~lvorahle phanna 'okinetic and toxieological profile suggc -t Repertaxin as a candidate for dinical cxploitation in prevention the deleterious con.sequences of the reperfllsion damage