Two distinct Ca2+ storage and release sites in human neutrophils

Abstract

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.

Control of Ca2+ influx in human neutrophils by inositol 1,4,5-trisphosphate (IP3) binding: differential effects of micro-injected IP3 receptor antagonists

“…One location was at a site that was accessible to both the high-and low-molecular-mass inhibitors and was responsible for Ca# + release. This was consistent with the previously identified Ca# + release site on the ' vestigial ' endoplasmic reticulum near the multi-lobed nucleus of the neutrophil [21][22][23]. The other IP $ -binding site was inhibitable only by the low-molecular-mass heparin and was involved in Ca# + influx.…”

Ca2+, calpain and 3-phosphorylated phosphatidyl inositides; decision-making signals in neutrophils as potential targets for therapeutics

“…The enzyme generates IP 3 (inositol trisphosphate) and diacylglycerol from PIP 2 (phosphatidyl inositol bisphosphate). IP 3 (or InsP(3)) diffuses away from the plasma membrane through the cytosol to a single juxta-nuclear site within the neutrophil, from where Ca 2 ‡ is released (Pettit et al 1997;Pettit & Hallett 1998). Blockade of IP 3 receptors results in an inhibition of Ca 2 ‡ release by these stimuli (Davies-Cox et al 2001).…”

Nonuniform Distribution of Ca2+ Uptake Sites within Human Neutrophils

“…This would be expected for a single uptake (or expulsion) mechanism. However, near the central juxtanuclear organelle, a faster Ca 2ϩ uptake mechanism was activated after a delay of about 3 s. A possible explanation is provided by that fact that at this site there is an identifiable Ca 2ϩ storage site (5,6,10). Presumably it has a constitutively active Ca 2ϩ SERCa pump to maintain high Ca 2ϩ within the store, and its effect on restoring local Ca 2ϩ to the resting level may be apparent due to the slow diffusion of Ca 2ϩ to this site.…”

“…In oocytes (2) and HeLa cells (3), Ca 2ϩ puffs can be detected which originate from specialised sites on the endoplasmic reticulum or discrete sites near the nucleus. In myeloid cells such as basophils (4) and neutrophils (5,6) there is also evidence for discrete Ca 2ϩ release sites. In neutrophils, there is a single Ca 2ϩ release site near the multilobed nucleus and also multiple release sites from the cytosol (5,6).…”

“…In myeloid cells such as basophils (4) and neutrophils (5,6) there is also evidence for discrete Ca 2ϩ release sites. In neutrophils, there is a single Ca 2ϩ release site near the multilobed nucleus and also multiple release sites from the cytosol (5,6). Neutrophils have no well defined endoplasmic reticulum, but at the central Ca 2ϩ release site, there is a vestigial membranous structure which stains with the "ER" marker DiOC 6 (3) (5, 6).…”