A study of the imbalance in B cell-expressed nucleoside triphosphate diphosphohydrolase 1-induced ADP degradation in graft injury during acute antibody-mediated rejection.

OBJECTIVE

To study the effects and mechanisms of the imbalance in B cell-expressed nucleoside triphosphate diphosphohydrolase 1 (NTPDase 1)-induced ADP degradation on graft injury during acute antibody-mediated rejection (AMR).

METHODS

The acute AMR animal model was established in male NTPDase 1-wild-type Balb/c nude mice. The levels of NTPDase 1 in B cells and NTPDase1 mRNA in grafted skin, changes in platelet activation markers and average platelet velocities were determined by luciferin/luciferase enzymatic, real-time fluorescent quantitative PCR, flow cytometry and inverted microscope. The pathological changes in grafted skin were observed by electron microscopy. The effects of pretreatment with different doses of exogenous NTPDase 1 on platelet activation and graft injury were studied.

RESULTS

The expression of B-cell NTPDase 1 was significantly increased at 30 min after the induction of acute AMR and restored to baseline levels after 7 days. The levels of NTPDase 1 mRNA in grafted skin were decreased at 30 min after the induction of acute AMR. After the induction of acute AMR, the levels of platelet activation markers increased significantly, whereas the average platelet velocity significantly decreased. After pretreatment with exogenous NTPDase 1, the expression of platelet activation markers significantly decreased, the average velocity of platelets increased significantly, and the necrosis of grafted skin and inflammatory reaction significantly reduced.

CONCLUSIONS

An imbalance in the NTPDase 1-induced degradation of extracellular ADP may be a major cause of graft injury in acute AMR. Pretreatment with exogenous NTPDase 1 may effectively inhibit platelet activation and protect grafted skin.