Cell-to-cell spread of calcium signals mediated by ATP receptors in mast cells

Abstract

Rat basophilic leukaemia cells, like mast cells from which they are derived, have surface Fc epsilon receptors that trigger secretion of inflammatory mediators when crosslinked. Both GTP-binding proteins and a rise in cytosolic calcium concentration ([Ca2+]i) are implicated in the secretory mechanism. Here we use a video-imaging technique to report that transient rises in [Ca2+]i initiated in an individual cell can spread from cell to cell in a wave-like pattern by means of a secreted intermediate, in the absence of gap-junctional communication. We find that the leukaemia cells, peritoneal mast cells and mucosal mast cells have cell-surface P2-type purinergic receptors that can trigger similar [Ca2+]i transients. We provide evidence that ATP is rapidly released, and that it can amplify [Ca2+]i signals and initial secretory responses during antigen-stimulation of rat basophilic leukaemia cells.

Mobilization of late-endosomal cholesterol is inhibited by Rab guanine nucleotide dissociation inhibitor

“…Figure 5a shows the distribution before (left panel), and 5 minutes after (right panel), ionomycin addition. This observed translocation of CaM is consistent with previously reported nuclear enrichment of CaM in other cell types [12,27,31,32]. Figure 5b shows that the CaM translocation to the nucleus is reversible when a transient calcium signal is applied.…”

“…As shown in measurements with the calcium indicator Fluo3-AM, stimulation of the P2-type purinergic receptor with ATP triggered brief individual calcium spikes (Figure 1a, left panel) [27], whereas crosslinking of the IgE Fc receptor (FcεRI) triggered repetitive calcium spikes or persistent increases in calcium concentration, depending on the concentration of antigen added and the particular cell studied (Figure 1a, center and right panels) [28,29]. The local concentration of free Ca 2+ -CaM corresponding to these different patterns of calcium signals was measured by expressing FIP-CB SM , an energy-transfer-based fluorescent indicator that binds Ca 2+ -CaM with 0.4 nM affinity.…”

P2 receptor-mediated signaling in mast cell biology

“…P2X 7 has a prominent expression in many immune cells, particularly lymphocytes, monocytes, macrophages, mast, dendritic, mesangial, and microglial cells as well as on a limited number of other cell types including parotid acinar cells, testis, and fibroblasts [17,38,40]. In addition to the cationic channel, the P2X 7 receptor may also induce the opening of a nonselective pore permeable to large organic molecules up to 900 Da [17,40].…”

“…Years later, families of P2Y and P2X purinergic receptors were cloned and characterized. Mast cells are not only a great source of ATP which is stored in their secretory granules and released upon stimulation [7], but they also express a variety of purinoceptors which trigger mast cell degranulation, cytokine secretion, chemotaxis, and apoptotic cell death [3,8,9]. In this review, we discuss the role of the P2 receptors and nucleotide signaling in mast cell biology.…”

Role of nitric oxide on purinergic signalling in the cochlea

“…Intercellular Ca 2+ waves play an important role in regulation of ciliary beat in airway epithelia [124], modulation of synaptic transmission by retinal astrocytes and Müller cells [125], coordination of metabolism by glial cells [126], control of vascular system by endothelial cells [127], and ossification by osteoblasts [128]. An extracellular propagation mode involving ATP as messenger has been identified [129,130]. Binding of extracellular ATP to P2Y receptors results in the production of intracellular inositol triphosphate (IP 3 ) and, consequently, an increase in [Ca 2+ ] i of contiguous and noncontiguous cells.…”