Injury by human complement causes large membrane lesions that reseal in IL-4-treated porcine endothelial cells

Abstract

Currently, successful xenotransplantation is restricted to theoretical conception due to the fact that an organism’s innate immune response rejects any tissue or organs transplanted from a different species. The complement system is a key component of this response in rejecting foreign substances, and mitigating the effects of this system could potentially revolutionize medical transplants. Complement system activation in an organism creates lesions in the membranes of foreign cells, leading to lysis and cell death. IL-4 is a cytokine, or a cell-signaling molecule, that seems to have a protective property against complement. Porcine endothelial cells first incubated in IL-4 exhibit decreased cell death after treatment with human complement, but the exact mechanism of protection is still unknown. A combination of the Neutral Red assay and the LDH assay were used to study cell recovery after complement treatment. Fluorescent microscopy was also used, in which labeled dextrans of different sizes were incubated with the cells along with complement. Should the mechanism of IL-4 protection be correctly identified, it may have potential uses in mitigating the innate immune response and the rejection of organs in xenotransplantation.