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First published online November 10, 2004

Journal of Cell Science 117, 2403e (2004)
© The Company of Biologists Limited
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In this issue

Eosinophil killing crystal clear...


Eosinophils are white blood cells that attack pathogens by releasing toxic proteins, including major basic protein (MBP) and eosinophil peroxidase. Quite how stimuli such as platelet-activating factor (PAF) induce the release of these from intracellular granules has been unclear. Scott O'Grady and co-workers now reveal the sequence of events that follows PAF stimulation (see p. 5749). They show that PAF signalling causes a rise in the level of intracellular Ca2+ ([Ca2+]i). Fluorescent pH indicators reveal that this leads to alkalinization of the cytoplasm, which can also be induced by compounds such as ionomycin and thapsigargin that increase [Ca2+]i by other mechanisms. Significantly, the authors find that the alkalinization of the cytoplasm is accompanied by acidification of the granules. Speculating that PAF-induced Ca2+ signalling might stimulate a proton pump in the granule membrane, they go on to demonstrate that an H+-ATPase pump is indeed present there. Since MBP is stored in granules as crystals whose solubilization requires low pH, the granule acidification pathway O'Grady and co-workers have uncovered probably plays a critical role in MBP release.


Related articles in JCS:

Platelet-activating factor stimulates cytoplasmic alkalinization and granule acidification in human eosinophils
Jennifer L. Bankers-Fulbright, Gail M. Kephart, Kathleen R. Bartemes, Hirohito Kita, and Scott M. O'Grady
JCS 2004 117: 5749-5757. [Abstract] [Full Text]  




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