BACKGROUND: Inflammation is one of major mechanisms contributing to the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. Pentraxin 3 (PTX3), produced in response to inflammatory signals, acts as a humoral arm of the innate immunity. Here we investigated the role of PTX3 produced from bone marrow-derived cells in myocardial I/R injury using PTX3-deficient (PTX3KO) mice. METHODS AND RESULTS: PTX3KO mice and wild-type littermate (WT) mice were lethally irradiated and injected with bone marrow (BM) cells, generating four types of mice (WT(WT-BM), WT(PTX3KO-BM), PTX3KO(WT-BM) and PTX3KO(PTX3KO-BM)). Six weeks after BM transplantation, the myocardial I/R procedure (45 min of left descending coronary artery ligation followed by 48 h of reperfusion) was performed. Infarct size was greater in WT and PTX3KO mice with BM from PTX3KO donor (WT(PTX3KO-BM) and PTX3KO(PTX3KO-BM)) compared with WT and PTX3KO mice with BM from WT donor (WT(WT-BM) and PTX3KO(WT-BM)). Localization of PTX3 was observed in neutrophils and macrophages in WT and PTX3KO mice with BM from WT donor (WT(WT-BM) and PTX3KO(WT-BM)), while only in endothelial cells in WT mice with BM from PTX3KO donor (WT(PTX3KO-BM)). Infiltration of neutrophils and generation of reactive oxygen species (ROS) at ischemic border zones were greater in PTX3KO mice with BM from PTX3KO donor (PTX3KO(PTX3KO-BM)) than PTX3KO mice with BM from WT donor (PTX3KO(WT-BM)). Plasma levels and cardiac expressions of interleukin-6 were higher in PTX3KO mice with BM from PTX3KO donor (PTX3KO(PTX3KO-BM)) than PTX3KO mice with BM from WT donor (PTX3KO(WT-BM)). However, no significant differences in infarct size, infiltration of neutrophils, generation of ROS and plasma and cardiac levels of interleukin-6 were observed between WT and PTX3KO mice with BM from WT donor and between WT and PTX3KO mice with BM from PTX3KO donor. These results indicated that the lack of PTX3 produced from BM-derived cells, and not from cardiac resident cells, exacerbated myocardial injury after I/R. CONCLUSION: PTX3 produced from bone marrow-derived cells plays a crucial role in cardiac protection against myocardial I/R injury by attenuating infiltration of neutrophils, generation of ROS and inflammatory cytokine.
BACKGROUND: Inflammation is one of major mechanisms contributing to the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. Pentraxin 3 (PTX3), produced in response to inflammatory signals, acts as a humoral arm of the innate immunity. Here we investigated the role of PTX3 produced from bone marrow-derived cells in myocardial I/R injury using PTX3-deficient (PTX3KO) mice. METHODS AND RESULTS: PTX3KO mice and wild-type littermate (WT) mice were lethally irradiated and injected with bone marrow (BM) cells, generating four types of mice (WT(WT-BM), WT(PTX3KO-BM), PTX3KO(WT-BM) and PTX3KO(PTX3KO-BM)). Six weeks after BM transplantation, the myocardial I/R procedure (45 min of left descending coronary artery ligation followed by 48 h of reperfusion) was performed. Infarct size was greater in WT and PTX3KO mice with BM from PTX3KO donor (WT(PTX3KO-BM) and PTX3KO(PTX3KO-BM)) compared with WT and PTX3KO mice with BM from WT donor (WT(WT-BM) and PTX3KO(WT-BM)). Localization of PTX3 was observed in neutrophils and macrophages in WT and PTX3KO mice with BM from WT donor (WT(WT-BM) and PTX3KO(WT-BM)), while only in endothelial cells in WT mice with BM from PTX3KO donor (WT(PTX3KO-BM)). Infiltration of neutrophils and generation of reactive oxygen species (ROS) at ischemic border zones were greater in PTX3KO mice with BM from PTX3KO donor (PTX3KO(PTX3KO-BM)) than PTX3KO mice with BM from WT donor (PTX3KO(WT-BM)). Plasma levels and cardiac expressions of interleukin-6 were higher in PTX3KO mice with BM from PTX3KO donor (PTX3KO(PTX3KO-BM)) than PTX3KO mice with BM from WT donor (PTX3KO(WT-BM)). However, no significant differences in infarct size, infiltration of neutrophils, generation of ROS and plasma and cardiac levels of interleukin-6 were observed between WT and PTX3KO mice with BM from WT donor and between WT and PTX3KO mice with BM from PTX3KO donor. These results indicated that the lack of PTX3 produced from BM-derived cells, and not from cardiac resident cells, exacerbated myocardial injury after I/R. CONCLUSION:PTX3 produced from bone marrow-derived cells plays a crucial role in cardiac protection against myocardial I/R injury by attenuating infiltration of neutrophils, generation of ROS and inflammatory cytokine.