The role of macrophages （MФ） as the first line of host defense is well accepted. These cells play a central role in orchestrating crucial functions during schistosomal infection. Thus, understanding the functional ...The role of macrophages （MФ） as the first line of host defense is well accepted. These cells play a central role in orchestrating crucial functions during schistosomal infection. Thus, understanding the functional diversity of these cells in the process of infection as well as the mechanisms underlying these events is crucial for developing disease control strategies. In this study, we adopted a Mqb polarization recognition system. M1 macrophage was characterized by expressing CD16/32, IL-12 and iNOS. M2 macrophage was characterized by expressing CD206, IL-10 and arg-1. In vivo （mouse peritoneal macrophages of different infection stages were obtained） and in vitro （different S. japonicum antigens were used to stimulate RAW264.7） were characterized by using the above mentioned system. NCA and ACA stimulated RAW264.7 express significantly higher levels of IL-12 while significantly higher levels of IL-10 were detected after soluble egg antigen （SEA） stimulation. The results showed that dramatic changes of antigen in the microenvironment before and after egg production led to macrophage polarization. Furthermore, through TLR blocking experiments, the TLR4 signaling pathway was found to play a role in the process of macrophage polarization toward M1. Our data suggest that macrophage polarization during S. japonicum infection had significant effects on host immune responses to S. japonicum.展开更多
Artemisinin-typed endoperoxides are a promising novel class of antischistosomal agents. Their antischistosomal activity is associated with high levels of intraceca toxic heme, which catalyzes the cleavage of the endop...Artemisinin-typed endoperoxides are a promising novel class of antischistosomal agents. Their antischistosomal activity is associated with high levels of intraceca toxic heme, which catalyzes the cleavage of the endoperoxide bridge to generate free radicals followed by such membrane damages as lipid peroxidation and protein denaturation. The interaction of the endoperoxides with heme also enhances heme-induced membrane toxicity by way of stimulating the redox activity of heme and preventing its polymerization to chemically inert pigment. Moreover, the drug-derivative radicals may disturb the parasites prooxidant-antioxidant balance, thereby sensitizing them to subsequent lethal damages of endogenous and exogenous oxidants increase. The free radicals-mediated mode of action of the endoperoxides may be used to explain such phenomena as sex difference and developmental stage difference in susceptibility to the endoperoxides as well as their slow schistosome killing.展开更多
文摘The role of macrophages （MФ） as the first line of host defense is well accepted. These cells play a central role in orchestrating crucial functions during schistosomal infection. Thus, understanding the functional diversity of these cells in the process of infection as well as the mechanisms underlying these events is crucial for developing disease control strategies. In this study, we adopted a Mqb polarization recognition system. M1 macrophage was characterized by expressing CD16/32, IL-12 and iNOS. M2 macrophage was characterized by expressing CD206, IL-10 and arg-1. In vivo （mouse peritoneal macrophages of different infection stages were obtained） and in vitro （different S. japonicum antigens were used to stimulate RAW264.7） were characterized by using the above mentioned system. NCA and ACA stimulated RAW264.7 express significantly higher levels of IL-12 while significantly higher levels of IL-10 were detected after soluble egg antigen （SEA） stimulation. The results showed that dramatic changes of antigen in the microenvironment before and after egg production led to macrophage polarization. Furthermore, through TLR blocking experiments, the TLR4 signaling pathway was found to play a role in the process of macrophage polarization toward M1. Our data suggest that macrophage polarization during S. japonicum infection had significant effects on host immune responses to S. japonicum.
文摘Artemisinin-typed endoperoxides are a promising novel class of antischistosomal agents. Their antischistosomal activity is associated with high levels of intraceca toxic heme, which catalyzes the cleavage of the endoperoxide bridge to generate free radicals followed by such membrane damages as lipid peroxidation and protein denaturation. The interaction of the endoperoxides with heme also enhances heme-induced membrane toxicity by way of stimulating the redox activity of heme and preventing its polymerization to chemically inert pigment. Moreover, the drug-derivative radicals may disturb the parasites prooxidant-antioxidant balance, thereby sensitizing them to subsequent lethal damages of endogenous and exogenous oxidants increase. The free radicals-mediated mode of action of the endoperoxides may be used to explain such phenomena as sex difference and developmental stage difference in susceptibility to the endoperoxides as well as their slow schistosome killing.
