An abnormal calcium uptake pump in Chediak-Higashi neutrophil lysosomes.

Calcium is mobilized from intracellular stores during phagocyte activation and appears to be involved in stimulus-response coupling in these and other cell types. Because the lysosome is a calcium-sequestering organelle in the neutrophil and abnormal lysosome morphology is associated with defective neutrophil function in Chediak-Higashi syndrome (CHS), we examined ATP-dependent calcium uptake in neutrophil lysosomes from the beige mouse model of CHS. We present findings indicating that CHS lysosomes have an enhanced capacity for ATP-dependent calcium uptake relative to control lysosomes. Kinetic analysis showed differences in Vmax and in the Km for both ATP and calcium, suggesting that both the number of lysosomal calcium uptake pumps and their substrate affinity may be altered in CHS. We conclude that a genetically determined abnormality of a subcellular calcium transport system may contribute to the structural and functional defects of CHS cells.