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.
Additional contributors: Barbara Benson; Agustin Dalmasso (faculty mentor)
Injury by human complement causes large membrane lesions that reseal in IL-4-treated porcine endothelial cells.
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