Eosinophils represent a subpopulation of white blood cells and belong together with neutrophils and basophils to the group of granulocytes. They are found in hematopoietic and lymphatic organs such as the bone marrow, spleen, lymph nodes and thymus, as well as in low numbers in the peripheral blood of healthy individuals. They also infiltrate, under physiological conditions, into several tissues, including the gastrointestinal tract, fat, ovaries, and uterus. Eosinophils contain cytoplasmic granules as a storage site for granule proteins and pro-inflammatory mediators which are released upon activation. Major basic protein (MBP) is one of the granule proteins and plays an important role in host defense against various microorganisms. Moreover, MBP is found in association with mitochondrial DNA (mtDNA) in eosinophil extracellular traps (EETs). Besides microorganisms, MBP exhibits noticeable cytotoxic effects in tissues as observed in different eosinophil-associated diseases. The mode of action for MBP toxicity has been previously shown to involve interactions with cell membranes but remains largely unknown. In this project, we aim to characterize membrane permeabilization and pore formation as mechanisms of toxicity mediated by MBP.
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