Abstract 10363: Cardio-Protective Effects of Pentraxin 3 Produced From Bone Marrow-Derived Cells Against Ischemia/Reperfusion Injury

Background: Pentraxin 3 (PTX3), produced in response to inflammatory signals, acts as a humoral arm of the innate immunity. Although a cardio-protective role of PTX3 against myocardial ischemia/reperfusion (I/R) injury has been reported experimentally, the origins of PTX3 functioning for protection of myocardium remain unclear. We examined the role of PTX3 produced from bone marrow (BM)-derived cells in myocardial I/R injury. Methods and Results: PTX3 deficient (PTX3 -/- ) and wild-type littermate (WT) mice were lethally irradiated and injected with BM cells, generating 4 types of mice (WT/WT BM, WT/PTX3 -/- BM, PTX3 -/- /WT BM and PTX3 -/- /PTX3 -/- BM). Six weeks after BM transplantation, the myocardial I/R procedure was performed. Infarct size was greater in WT and PTX3 -/- mice with BM from PTX3 -/- donor (WT/PTX3 -/- BM and PTX3 -/- /PTX3 -/- BM) compared with WT and PTX3 -/- mice with BM from WT donor (WT/WT BM and PTX3 -/- /WT BM) (P<0.05 and P<0.01, respectively). Localization of PTX3 was observed in neutrophils and macrophages in WT and PTX3 -/- mice with BM from WT donor (WT/WT BM and PTX3 -/- /WT BM), while only in endothelial cells in WT mice with BM from PTX3 -/- donor (WT/PTX3 -/- BM). Infiltration of neutrophils and generation of reactive oxygen species (ROS) at ischemic border zones were greater in PTX3 -/- mice with BM from PTX3 -/- donor (PTX3 -/- /PTX3 -/- BM) than PTX3 -/- mice with BM from WT donor (PTX3 -/- /WT BM) (P<0.01 and P<0.01, respectively). Plasma levels and cardiac expressions of IL-6 were higher in PTX3 -/- mice with BM from PTX3 -/- donor (PTX3 -/- /PTX3 -/- BM) than PTX3 -/- mice with BM from WT donor (PTX3 -/- /WT BM) (P<0.05 and P<0.05, respectively). However, no significant differences in infarct size, infiltration of neutrophils, generation of ROS and production of IL-6 were observed between WT and PTX3 -/- mice with BM from WT donor and between WT and PTX3 -/- mice with BM from PTX3 -/- donor. These results indicate that the lack of PTX3 produced from BM-derived cells, but not from cardiac resident cells, contributes to neutrophil infiltration, ROS generation and IL-6 production in response to I/R, resulting in the increment of infarct size. Conclusion: PTX3 produced from BM-derived cells plays a crucial role in cardiac protection against myocardial I/R injury.