In response to a chemotactic gradient, leukocytes extravasate and chemotax toward the site of pathogen invasion. Although fundamental in the control of many leukocyte functions, the role of cytosolic free Ca2+ in chemotaxis is unclear and has been the subject of debate. Before becoming motile, the cell assumes a polarized morphology, as a result of modulation of the cytoskeleton by G protein and kinase activation. This morphology may be reinforced during chemotaxis by the intracellular redistribution of Ca2+ stores, cytoskeletal constituents, and chemoattractant receptors. Restricted subcellular distributions of signaling molecules, such as Ca2+, Ca2+/calmodulin, diacylglycerol, and protein kinase C, may also play a role in some types of leukocyte. Chemotaxis is an essential function of most cells at some stage during their development, and a deeper understanding of the molecular signaling and structural components involved will enable rational design of therapeutic strategies in a wide variety of diseases.

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in response to N-formyl-methionyl-leucyl-phenylalanine, whereas engagement and clustering of CD11b/CD18 integrins causes Ca 2؉ release from the peripheral stores. The release sites also correlated with organelles that stained with DiOC 6 (3). Localized phototoxicity generated by DiOC 6 (3) excitation resulted in inhibition of the release of stored Ca 2؉ , which was selective for the stimulus used. The presence of two distinct cellular locations for these Ca 2؉ stores and their independent release raises the possibility that separate intracellular messengers for their release are generated.

Characterization of early Ca2+ signalling events is crucial for understanding the mechanisms which lead to cell signalling. Rapid confocal laser scanning of Fluo3-loaded neutrophils was used to provide spatially resolved cytosolic free Ca2+ measurements from neutrophils stimulated with formyl-Met-Leu-Phe with a time resolution of 12.5 ms. Heterogeneity of the magnitude and timing of the response was observed between individual neutrophils. There was always a delay between contact with the stimulus and onset of the Ca2+ signal, with a minimum delay of 75 ms and a mean delay of 530 ms (n = 150). There was no delay in the cytosolic free Ca2+ rise induced by ionomycin. The earliest Ca2+ event detected following stimulation with formyl-Met-Leu-Phe (1 microM) was a localized rise in cytosolic free Ca2+ from a location within the cell, pointing to Ca2+ store release as the initial event for triggering whole-cell Ca2+ changes in these cells.

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