The complement system is a part of the innate immune system in the fluid phase and efficiently eliminates pathogens. However, its activation requires tight regulation on the host cell surface in order not to compromise cellular viability. Previously, we showed that loss of placental cell surface sialylation in mice in vivo leads to a maternal complement attack at the fetal-maternal interface, ultimately resulting in loss of pregnancy. To gain insight into the regulatory function of sialylation in complement activation, we here generated trophoblast stem cells devoid of sialylation, which also revealed complement sensitivity and cell death in vitro. Glycolipid-analysis by xCGE-LIF allowed us to identify the monosialoganglioside GM1a as a key element of cell surface complement regulation. Exogenously administered GM1a integrated into the plasma membrane of trophoblasts, dramatically increased binding of complement factor H and was sufficient to protect the cells from complement attack and cell death. Furthermore, GM1a treatment rescued sensitized human erythrocytes and endothelial cells from complement attack in a concentration dependent manner. This study demonstrates for the first time the complement regulatory potential of exogenously administered gangliosides and paves the way for sialoglycotherapeutics as a novel substance class for membrane-targeted complement regulators.
As a severe danger to potato plants, potato cyst nematodes (PCNs) are regulated quarantine pests in many countries. Adhering soils to potato or other tuber crops provoke the uncontrolled spread of the pest after their industrial processing. The disinfection of soil tares to inactivate PCNs is therefore compulsory. In the present study, we test whether the viability and formation of PCN cysts are suppressed after treatment with γ and β irradiation. In a first experiment, nematode cysts were treated with γ or β irradiation without soil matrix to determine the minimum dose parameters in a range between 0–12 kGy. Subsequently, two representative soils that included cysts were irradiated. Irradiation effects on PCN viability and the formation of new cysts were evaluated via hatching tests and bioassays with susceptible potato plants, respectively. In addition, maize seedling growth was tested in irradiated soil tares. We found that next to γ also, β irradiation suppressed the hatch of PCN juveniles and its formation of cysts when placed in soil tares. The growth of maize seedlings was not impaired in irradiated soils compared to control soils. Both γ and β irradiation treatment offer an organism group selective and effective phytosanitary measures to disinfect soil tares from PCNs.
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