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PubMed1995

Irsogladine inhibits ionomycin-induced decrease in intercellular communication in cultured rabbit gastric epithelial cells.

Effects of irsogladine on ionomycin-induced decrease in intercellular communication and increase in intracellular concentration of Ca2+ ([Ca2+]i) were investigated in cultured rabbit gastric epithelial cells. Ionomycin (10(-7)-10(-6) M) transiently and concentration-dependently inhibited intercellular communication concomitantly with the elevation of [Ca2+]i in the presence and absence of extracellular Ca2+. Irsogladine (10(-5) M), which has been shown to facilitate intercellular communication, suppressed the ionomycin-induced elevation of [Ca2+]i and decrease in intercellular communication. The suppression of the ionomycin effects by irsogladine was independent of extracellular Ca2+. TMB-8 [8-(diethylamino)octyl-3,4,5-trimethoxy-benzoate hydrochloride] (10(-6) M) also suppressed the ionomycin-induced elevation of [Ca2+]i and decrease in intercellular communication. These results indicate that the ionomycin-induced decrease in intercellular communication may be due to Ca2+ mobilization from intracellular stores. Inhibitory effects of irsogladine and TMB-8 on the ionomycin-induced decrease in intercellular communication may be produced by suppressing Ca2+ mobilization.

Animals↗
PubMed1992

Regulation of cell division of mature B cells by ionomycin and phorbol ester.

The growth of a human B lymphoma cell line B104, an experimental model for mature B cells, was inhibited by ionomycin but not 12-O-tetradecanoylphorbol-13-acetate (TPA). Ionomycin inhibited B104 cells from entering into the M phase of the cell cycle without affecting DNA synthesis. The inhibition of cell division of B104 cells by ionomycin occurred within 24 h after stimulation. Because such a mode of action resembles that of anti-IgM antibodies, signals transduced by Ca2+ may be responsible for the inhibition of cell division of B104 cells by anti-IgM antibodies. Indeed, EGTA suppressed the inhibition of cell division of B104 cells caused not only by ionomycin, but also by anti-IgM antibody. Although TPA itself did not have any ability to promote the growth of B104 cells, it could cancel the inhibition of cell division of B104 cells by ionomycin and increase the proportion of B104 cells entering into the M phase of the cell cycle. Staphylococcus aureus Cowan I causes the greatest proliferation of normal human peripheral blood B cells during the period from 48 to 72 h after stimulation. When ionomycin was added to S. aureus Cowan I-stimulated peripheral blood B cells at 48 h of culture, it inhibited cell division during this period without affecting DNA synthesis. In the presence of TPA, this activity of ionomycin was suppressed, and the proportion of M-phase cells increased. These results suggest that cell division of mature B cells is regulated by the signals mediated by Ca2+ and protein kinase C in a mode quite different from that of regulation of DNA synthesis.

B-Lymphocytes↗
PubMed1989

Mechanisms of T cell activation by the calcium ionophore ionomycin.

We have investigated signaling mechanisms that may underlie the T cell mitogenic properties of the Ca2+ ionophore ionomycin. Ionomycin induces highly purified resting human T cells to proliferate in the presence of monocytes with accompanying IL-2R expression and IL-2 synthesis. Treatment of T cells with ionomycin triggers the hydrolysis of phosphoinositides, as evidenced by the accumulation of the hydrolytic by-products phosphatidic acid and inositol phosphates. Ionomycin also induces the activation of protein kinase C (PKC), as demonstrated by the auto-phosphorylation of PKC and the phosphorylation of the PKC target proteins CD4 and CD8. Ionomycin synergizes with PMA in enhancing the activation of PKC. It is concluded that, in addition to its putative activation of Ca2+/calmodulin-dependent signaling pathways, ionomycin induces the hydrolysis of phosphoinositides and the activation of PKC in human T cells. The synergy of ionomycin with phorbol esters in triggering T cell activation may relate, at least in part, to enhanced activation of PKC.

Calcium↗
PubMed1980

Cation transport and specificity of ionomycin. Comparison with ionophore A23187 in rat liver mitochondria.

Based on the effects of ionomycin upon mitochondrial respiration, ionomycin was shown to be an effective ionophore for Ca2+ in rat liver mitochondria. The ionomycin-induced efflux of Ca2+ across the inner membrane was more sensitive to loading the mitochondria with Ca2+ than was efflux catalyzed by A23187. At saturating concentrations of Ca2+, the turnover number for ionomycin was 3- to 5-fold greater than that of A23187. Ionomycin catalyzed the efflux of mitochondrial Mg2+ at rates comparable to those observed with A23187. Ionomycin also mediated an efflux of K+ provided that the mitochondria were depleted of their endogenous divalent metal ions. The apparent turnover numbers for K+ efflux suggest that ionomycin is more specific for divalent metal ions than A23187.

Animals↗
PubMed1996

Ionomycin-stimulated arachidonic acid release in human platelets: a role for protein kinase C and tyrosine phosphorylation.

Collagen (10-90 micrograms/ml) and ionomycin (1 microM; a calcium ionophore) each evoked rises in intracellular free calcium, protein kinase C activity and arachidonic acid release in human platelets, and as previously demonstrated for collagen, ionomycin (1 microM) stimulated protein tyrosine phosphorylation. However, at lower concentrations (60 and 250 nM) ionomycin selectively mobilised calcium. Ro31-8220 (a selective inhibitor of protein kinase C) inhibited (by 50%) ionomycin-stimulated arachidonic acid release. Genistein (an inhibitor of protein tyrosine kinases) also reduced by 50% ionomycin-stimulated arachidonic acid release. In combination, genistein and Ro31-8220 abolished ionomycin-stimulated arachidonic acid release. These findings show 1) that a rise in calcium is not sufficient, and 2) the activation of both protein kinase C and protein tyrosine phosphorylation is necessary, for full ionomycin-stimulated arachidonic acid release in human platelets.

Arachidonic Acid↗
PubMed1987

Induction of human B cell proliferation and differentiation by the combination of phorbol ester and ionomycin.

Phorbol esters and Ca2+ ionophores are known to mimic intracellular messengers involved in cell activation. We studied the effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) and ionomycin on tonsil and peripheral blood-derived B lymphocytes. We show that TPA and ionomycin are co-mitogenic and induce B lymphocyte differentiation. Although TPA in high concentrations is mitogenic to B lymphocytes by itself, submitogenic concentrations of TPA in combination with ionomycin trigger 50% of B lymphocytes to synthesize DNA. Stimulation of B lymphocytes with TPA plus ionomycin resulted in increased magnitude and a shift in the kinetics of c-fos and c-myc expression compared with either agent used alone. Activation markers such as the transferrin and interleukin 2 (IL2) receptors were markedly increased after 24 h incubation with TPA and ionomycin. In parallel to the rapid proliferative burst, we observed evidence for B lymphocyte differentiation with an increase in the number of cells expressing cytoplasmic immunoglobulin (Ig) and the disappearance of the B1 surface marker. Since the cells remained surface Ig+ and secreted only small quantities of Ig, our results suggest that the combination of TPA and ionomycin is a potent inducer of B cell proliferation and early differentiation; terminal differentiation to an Ig-secreting state, however, is not achieved.

Antigens, Surface↗
PubMedDate not supplied

Effects of the divalent cation ionophore ionomycin on the performance of isolated guinea-pig atria.

In isolated electrically driven left and in spontaneously beating right guinea-pig atria, the calcium ionophore ionomycin produced a concentration-dependent positive inotropic and chronotropic effect with a threshold near 10(-7) mol/l and a pD2 of 6.31 +/- 0.09 and 5.94 +/- 0.07, respectively. At low [Ca2+]o (0.5 mmol/l), the positive inotropic effect of ionomycin (3 X 10(-6) mol/l) was strongly attenuated by ryanodine and nifedipine, and slightly attenuated by pindolol and mepyramine; atropine had no effect. The positive chronotropic effect of ionomycin was slightly reduced by cimetidine or pindolol, whereas atropine, nifedipine, and ryanodine showed no inhibitory activity. The oxygen consumption of resting left atria was significantly enhanced by addition of ionomycin. It is concluded that the action of ionomycin involves at least the following mechanisms: I) release of Ca2+ from sarcoplasmic reticulum, II) influx of Ca2+ from the extracellular space, and, having little significance, III) release of catecholamines and histamine from sympathetic nerve endings and tissue mast cells. However, additional mechanisms of action of ionomycin cannot be excluded.

Animals↗
PubMed1988

Glycoprotein biosynthesis in B lymphocytes: induction of protein N-glycosylation, RNA synthesis, and DNA synthesis by phorbol ester plus ionomycin is blocked by protein kinase inhibitors.

The combination of phorbol 12-myristate 13-acetate (PMA) and ionomycin produces a dramatic increase in the incorporation of [2-3H]mannose into Glc3Man9GlcNAc2-P-P-dolichol and glycoprotein, and the induction of RNA and DNA synthesis in murine splenic B lymphocytes (B cells). The kinetics of the induction processes and the concentrations of PMA and ionomycin required for the optimal response have been defined. While the levels of induction of RNA and DNA synthesis by PMA + ionomycin were similar to the mitogenic response to bacterial lipopolysaccharide, activation by PMA and the calcium ionophore resulted in a threefold higher stimulation in dolichol-linked oligosaccharide biosynthesis and protein N-glycosylation. These results indicate that all signalling mechanisms that trigger RNA and DNA synthesis may not be sufficient to produce maximal induction of the N-glycosylation apparatus. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H-7), a potent protein kinase C inhibitor, prevented the induction of protein N-glycosylation activity (IC50 = 11 microM), as well as RNA (IC50 = 18 microM) and DNA synthesis (IC50 = 12 microM), two common indices of B cell activation. N-[2-(Methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) also inhibited the induction of oligosaccharide-lipid intermediate, glycoprotein, RNA, and DNA synthesis, but required higher concentrations than H-7 for 50% inhibition. N-(2-Guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), a potent inhibitor of cyclic nucleotide-dependent protein kinases, had little effect on the activation of the B cell metabolic processes. The H-7-sensitive reactions involved in the induction of RNA and DNA synthesis occurred within 4 h, but induction of lipid intermediate and glycoprotein biosynthesis remained sensitive to H-7 for 10 h after exposure to PMA and ionomycin. Direct in vitro assays in the presence of 0.6% Brij 58 reveal that a cytosolic, phospholipid-dependent protein kinase activity is translocated to a membrane site(s) after treatment with PMA and ionomycin, and the translocated protein kinase is sensitive to H-7. The relative order of potency of the protein kinase inhibitors on the metabolic processes strongly supports the hypothesis that protein kinase C, acting synergistically with Ca2+ mobilization, plays a key regulatory role in the early stages of B cell activation. The synthesis of oligosaccharide-lipid intermediates and protein N-glycosylation are also shown to be induced in B cells activated by PMA + ionomycin.

Animals↗
PubMed1990

Molecular signals in B cell activation. II. IL-2-mediated signals are required in late G1 for transition to S phase after ionomycin and PMA treatment.

We report that sustained increase of intracellular calcium ion concentration and protein kinase C (PKC) activation maintained throughout the G1 phase of cell cycle do not provide sufficient signals to cause S-phase entry in rabbit B cells, and that additional signals transduced by IL-2 and IL-2 receptor interaction are essential for G1 to S transition. We have shown earlier that rabbit B cells can be activated to produce IL-2 and express functional IL-2 receptors after treatment with ionomycin and PMA. Herein we have compared the response of rabbit PBLs, which contain about 50% T cells, with those of purified B cells. After activation with ionomycin or PMA, comparable numbers of PBLs and B cells entered the cell cycle; but DNA synthesis by the PBL cultures was three to four times higher than that of cultures of purified B cells. Interestingly, IL-2 production by the PBL cultures was also three to four times higher than in B cell cultures, suggesting an involvement of IL-2 in inducing DNA synthesis in these cells. The hypothesis that IL-2, which is produced in early G1, acts in late G1 and is required for G1 to S transition in B cells was supported by the following observations: (i) IL-2 production by B cells was detected as early as 6 hr after activation and preceded DNA synthesis by at least 24 hr. (ii) B cell blasts in G1 (produced by treatment of resting B cells with ionomycin and PMA) showed DNA synthesis in response to IL-2, but showed very little DNA synthesis in response to restimulation with ionomycin and PMA. (iii) A polyclonal rabbit anti-human IL-2 antibody caused nearly complete inhibition of DNA synthesis by B cells activated by ionomycin and PMA. (iv) A PKC inhibitor, K252b, inhibited DNA synthesis in ionomycin and PMA-stimulated cells if added at the beginning of culture but was not inhibitory if added 16 hr later. We conclude that increased [Ca2+]i and PKC activation are not sufficient signals for G1 to S transition in B cells; entry into S is signaled by IL-2, and IL-2-mediated signal transduction probably does not involve increased [Ca2+]i or PKC activation.

Animals↗
PubMed1992

Effects of phorbol myristate and ionomycin on in vitro growth of aged Peyer's patch T and B cells.

The proliferative responses of Peyer's patch (PP) T cells from aged BALB/c mice to concanavalin A (Con A) are considerably reduced, as compared to those of the young (P < 0.001). This reduced reactivity of aged T cells could be partly, but not entirely, corrected by interleukin 2 (IL-2) (P < 0.001). PP T cells from aged mice responded synergistically to a protein kinase C (PKC) activator, phorbol myristate acetate (PHA), plus a calcium ionophore, ionomycin, at much lower concentrations than to Con A (P < 0.001); however, the maximal proliferative response still remained nearly at 8/10th of the young (P < 0.01) and higher levels of PMA (but not of ionomycin) were required (P < 0.001). Addition of IL-2 restored the diminished response to the levels of the young T cells (P < 0.05), but that of Con A did not (P > 0.05). The proliferative responses of PP B cells to lipopolysaccharide (LPS) do not differ from those of the young (P > 0.05), but the spontaneous proliferation of aged (unstimulated) B cells is enhanced nearly twofold versus that of the young (P < 0.001). Like the PP T cells, PP B cells from aged mice also responded synergistically to PMA plus ionomycin but to a lesser degree than those of the young under the same stimulation (P < 0.01). Their maximal proliferation required higher levels of PMA, but not of ionomycin and was also diminished (P < 0.01), compared to that of the young. B cell stimulatory co-factors, IL-4 and IL-6, failed to affect the response of aged and young B cells to PMA plus ionomycin (P > 0.05), whereas LPS remediates the reduced response of aged B cells to PMA plus ionomycin. Thus, T and B cells from senescent PP demonstrate an impaired proliferative responsiveness via the Ca-dependent PKC pathway. A T cell mitogen and B cell stimulatory cytokines did not alter this activation pathway, once optimally stimulated. Whereas, T cell stimulatory cytokine IL-2 and B cell mitogen LPS could restore the age-associated decline of the corresponding lymphocyte subsets, T and B cells, in activation of the Ca-dependent pathway. The altered transmembrane signal transduction appears to be intrinsically defective in these aged PP T and B cells.

Aging↗
PubMed1989

Ionomycin releases calcium from the sarcoplasmic reticulum and activates Na+/Ca2+ exchange in vascular smooth muscle cells.

Ionomycin (1 microM) produced a large spike in cytosolic free Ca2+ [( Ca2+]i). The ionophore had no effect on [Ca2+]i if the sarcoplasmic reticulum had previously been Ca2+ depleted by stimulating neurohormone receptors. Ionomycin markedly increased 45Ca2+ efflux and decreased total cell Ca2+ by 60 to 70% in 1 min. Replacing extracellular Na+ [( Na+]o) with choline or N-methyl-D-glucamine strongly inhibited the effects of ionomycin on 45Ca2+ efflux and total Ca2+. Ionomycin caused similar peak increases in [Ca2+]i in the presence and absence of [Na+]o, but the exponential fall from the peak was faster in the presence of [Na+]o. Dimethylbenzamil, a potent blocker of Na+/Ca2+ exchange in these cells, strongly inhibited the effects of ionomycin on 45Ca2+ efflux and total cell Ca2+. We conclude that the increase in cytosolic free Ca2+ produced by ionomycin may be sufficient to activate the plasma membrane Na+/Ca2+ exchanger which removes Ca2+ from the cytosol and helps restore basal [Ca2+]i.

Amiloride↗
PubMed1990

Lipoxygenase inhibitors suppress intracellular calcium rise induced by ionomycin in rat thymocytes.

The lipoxygenase (LO) inhibitors nordihydroguaiaretic acid (NDGA) and 15S-hydroxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-HETE) have been found to suppress the rise in free cytoplasmic Ca2+ concentration [( Ca2+]i) induced by the Ca2+ ionophores ionomycin and A23187 in rat thymocytes. Bromophenacyl bromide (BPB), a phospholipase A2 (PLA2) inhibitor, produced a much weaker inhibitory effect, and indomethacin, a cyclo-oxygenase inhibitor, practically did not influence the [Ca2+]i response to ionomycin. These findings implicate the involvement of LO product(s) in the [Ca2+]i rise triggered by the Ca2+ ionophores. The contribution of the NDGA-sensitive component to the ionomycin-induced [Ca2+]i rise was significant in the ionomycin concentration range of 0.1 nM to 0.1 microM whereas at higher doses of the ionophore it gradually diminished. By contrast, the [Ca2+]i rise induced by exogenous arachidonic acid (AA) or melittin, a PLA2 activator, was not suppressed but potentiated by NDGA. Ionomycin and exogenous AA also elicited opposite changes in thymocyte cytoplasmic pH (pHi): the former elevated the pHi while the latter induced a pronounced acidification of the cytoplasm. This difference in the pHi responses may account for the different sensitivity of ionomycin- and AA-elicited [Ca2+]i signal to LO inhibitors.

Acetophenones↗
PubMed1985

Pancreatic amylase secretion and cytoplasmic free calcium. Effects of ionomycin, phorbol dibutyrate and diacylglycerols alone and in combination.

Both protein kinase C and Ca2+ may act in concert to bring about activation of secretion. This study examined the actions on pancreatic acini of ionomycin and phorbol dibutyrate, which selectively stimulate one or the other of these pathways; their stimulatory effects were compared with those of receptor agonists, such as carbachol and caerulein, which activate phospholipase C. The Ca2+ ionophore ionomycin produced a dose-dependent increase in amylase secretion and intracellular free Ca2+ (as measured by quin-2). The increase in amylase secretion elicited by carbachol or caerulein was accompanied by a small sustained increase in intracellular free Ca2+, following an initial peak. However, the elevation in intracellular free Ca2+ produced by these receptor agonists for a given level of amylase secretion was less than that observed with ionomycin. Phorbol dibutyrate stimulated amylase secretion by a mechanism that was independent of extracellular Ca2+, and no change in intracellular free Ca2+ was observed. Synergistic stimulatory effects of phorbol dibutyrate and ionomycin were observed, whether the phorbol ester was present before, or in combination with, ionomycin. Diacylglycerols containing unsaturated fatty acids (1,2-dioleoylglycerol and 1,3-dioleoylglycerol) also stimulated amylase secretion and exhibited synergistic effects on secretion with ionomycin. These findings suggest that complete activation of amylase secretion from the pancreas requires stimulation of both Ca2+-dependent and protein kinase C-activated pathways.

Amylases↗
PubMed2000

Ionomycin, a carboxylic acid ionophore, transports Pb(2+) with high selectivity.

Studies utilizing phospholipid vesicle loaded with chelator/indicators for polyvalent cations show that ionomycin transports divalent cations with the selectivity sequence Pb(2+) > Cd(2+) > Zn(2+) > Mn(2+) > Ca(2+) > Cu(2+) > Co(2+) > Ni(2+) > Sr(2+). The selectivity of this ionophore for Pb(2+) is in contrast to that observed for A23178 and 4-BrA23187, which transport Pb(2+) at efficiencies that are intermediate between those of other cations. When the selectivity difference of ionomycin for Pb(2+) versus Ca(2+) was calculated from relative rates of transport, with either cation present individually and all other conditions held constant, a value of approximately 450 was obtained. This rose to approximately 3200 when both cations were present and transported simultaneously. 1 microM Pb(2+) inhibited the transport of 1 mM Ca(2+) by approximately 50%, whereas the rate of Pb(2+) transport approached a maximum at a concentration of 10 microM Pb(2+) when 1 mM Ca(2+) was also present. Plots of log rate versus log ionomycin or log Pb(2+) concentration indicated that the transporting species is of 1:1 stoichiometry, ionophore to Pb(2+), but that complexes containing an additional Pb(2+) may occur. The species transporting Pb(2+) may include H.IPb.OH, wherein ionomycin is ionized once and the presence of OH(-) maintains charge neutrality. Ionomycin retained a high efficiency for Pb(2+) transport in A20 B lymphoma cells loaded with Indo-1. Both Pb(2+) entry and efflux were observed. Ionomycin should be considered primarily as an ionophore for Pb(2+), rather than Ca(2+), of possible value for the investigation and treatment of Pb(2+) intoxication.

Aminoquinolines↗
PubMed2001

Ionomycin causes activation of p38 and p42/44 mitogen-activated protein kinases in human neutrophils.

Many receptor-linked agents that prime or activate the NADPH oxidase in polymorphonuclear neutrophils (PMNs) elicit changes in cytosolic Ca2+ concentration and activate mitogen-activated protein (MAP) kinases. To investigate the role of Ca2+ in the activation of p38 and p42/44 MAP kinases, we examined the effects of the Ca2+-selective ionophore ionomycin on priming and activation of the PMN oxidase. Ionomycin caused a rapid rise in cytosolic Ca2+ that was due to both a release of cytosolic Ca2+ stores and Ca2+ influx. Ionomycin also activated (2 microM) and primed (20-200 nM) the PMN oxidase. Dual phosphorylation of p38 MAP kinase and phosphorylation of its substrate activating transcription factor-2 were detected at ionomycin concentrations that prime or activate the PMN oxidase, while dual phosphorylation of p42/44 MAP kinase and phosphorylation of its substrate Elk-1 were elicited at 0.2-2 microM. SB-203580, a p38 MAP kinase antagonist, inhibited ionomycin-induced activation of the oxidase (68 +/- 8%, P < 0.05) and tyrosine phosphorylation of 105- and 72-kDa proteins; conversely, PD-98059, an inhibitor of MAP/extracellular signal-related kinase 1, had no effect. Treatment of PMNs with thapsigargin resulted in priming of the oxidase and activation of p38 MAP kinase. Chelation of cytosolic but not extracellular Ca2+ completely inhibited ionomycin activation of p38 MAP kinase, whereas chelation of extracellular Ca2+ abrogated activation of p42/44 MAP kinase. These results demonstrate the importance of changes in cytosolic Ca2+ for MAP kinase activation in PMNs.

Activating Transcription Factor 2↗
PubMed1982

Ionomycin stimulates secretion of catecholamines from cat adrenal gland and spleen.

Ionomycin, a polyether antibiotic, stimulated the secretion of catecholamines and dopamine beta-hydroxylase from perfused adrenal glands and [3H]norepinephrine ([3H]NE) from spleens of the cat. Release was calcium dependent, and strontium or barium did not substitute for calcium. Ionomycin failed to release [3H]NE from reserpinized spleens. High magnesium did not interfere in the ionomycin response, but lanthanum and manganese blocked it. Ionomycin response that was pH dependent was not affected by potassium depolarization. The secretory response to ionomycin was enhanced when both glycolysis and oxidative metabolism were inhibited. It is concluded that ionomycin introduces calcium into the chromaffin cells and adrenergic nerve terminals to cause the secretory response and that a rise in intracellular calcium may be an adequate stimulus for secretion.

Adrenal Glands↗
PubMed1991

Induction of T cell CD7 gene transcription by nonmitogenic ionomycin-induced transmembrane calcium flux.

The CD7 molecule is a 40-kDa member of the Ig superfamily that has structural homology to the murine Thy-1 molecule and is acquired early in human T cell ontogeny. Previous studies have demonstrated that expression of the CD7 molecule is markedly up-regulated during T cell activation. In this study, we have studied the signals required for CD7 up-regulation on human T cells. We found that nonmitogenic amounts of ionomycin selectively and maximally up-regulated T cell CD7 on mature (peripheral blood) T cells after 24 h. Whereas CD7 expression was increased 78 +/- 25% by 0.5 microM ionomycin, expression of CD25 (IL-2R alpha), class II MHC, 4F2, transferrin receptor, CD2, CD3, CD4, CD5, and CD8 molecules was not increased. Ionomycin-induced CD7 surface expression was associated with peak increases in CD7 mRNA after 4 to 6 h. Transcriptional analysis and CD7 mRNA half-life determination revealed the increase in CD7 mRNA was the result of increased CD7 gene transcription 1 h after ionomycin stimulation and was not due to prolongation of CD7 mRNA half-life. The up-regulation of surface CD7 expression by ionomycin was dependent on extracellular calcium and did not require the activation of T cell tyrosine protein kinase. Mitogenic CD2 and CD3 mAb as well as stimulation of T cells by PHA also up-regulated CD7 expression. CD7 up-regulation by ionomycin was transient (24 to 72 h) and inhibitable by cyclosporin A, whereas CD7 up-regulation by PHA was sustained over 5 to 7 days and was significantly less inhibitable by cyclosporin A. These data demonstrate that induction of a transmembrane calcium flux generates signals that lead to CD7 gene transcription.

Antibodies, Monoclonal↗
PubMedDate not supplied

The role of external and internal free Ca2+ concentration on ionomycin induced leukotriene C4 formation in rat basophilic leukemia cells.

Rat basophilic leukemia (RBL-2H3) cells serve as a model to examine the role of external and internal free Ca2+ concentration [Ca2+]i, following ionomycin induced stimulation of leukotriene C4 (LTC4) formation. Brief exposure of RBL cells to Ca(2+)-free medium abolished the effect of ionomycin on elevation of [Ca2+]i (monitored by Quin-2/AM) and on stimulation of LTC4 production. In Ca(2+)-rich medium (1.8 mM) however there was a large increase in both parameters. We showed recently (Her et al., 1990) that hydrocortisone (HC) and dexamethasone markedly suppressed the elevated [Ca2+]i induced by antigen. Following HC pretreatment, there was a modest (35%) suppression of [Ca2+]i elevation induced by submaximal (0.1 microM) as well as maximal (1 microM) doses of ionomycin (nevertheless, 8 fold increase above basal level was still observed), LTC4 formation, however, was only inhibited (47%) by HC when induced by submaximal dose of ionomycin, but not that induced by higher doses of ionomycin. Phorbol ester (TPA) abolished elevation of [Ca2+]i induced by antigen. Short treatment with TPA had a modest inhibitory (28%) effect on elevation of [Ca2+]i and on LTC4 formation (23%) induced by ionomycin. It is proposed that high [Ca2+]i, possibly originated mainly from extracellular source, is essential for induction of LTC4 formation.

Animals↗