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Copper (Cu) is essential for innate immunity; however, how neutrophils regulate Cu
homeostasis to support their functions remains unclear. We found that myeloid
progenitors express abundant Cu-transporter ATP7B targeted to distinct vesicles and
store Cu in vesicles. During neutrophil differentiation, ATP7B is downregulated, whereas
ATP7A, LOXL2, and SLC31A2 are induced, suggesting a coordinated switch from Cu
storage to utilization. As mature neutrophils exit the bone marrow, cellular Cu levels drop
markedly, indicating Cu release during late maturation or egress. Myeloid-specific
deletion of Atp7b in mice uncouples lineage commitment from functional maturation:
Atp7b-deficient cells differentiate into neutrophils but fail to mature fully, showing more
mitochondria, fewer lysosome-like structures, lower abundance of Cebp-ε and Ngal,
reduced tubulin levels, and disrupted microtubules. Following lipopolysaccharide
injection, Atp7b-deficient bone marrow releases fewer neutrophils into the bloodstream.
Together, these findings reveal a previously unrecognized role of the Cu-transport
network in neutrophil maturation and egress.
March |