Modulation of histamine release from canine fundic mucosal mast cells

1988 ◽  
Vol 254 (1) ◽  
pp. G40-G48 ◽  
Author(s):  
A. H. Soll ◽  
M. Toomey ◽  
D. Culp ◽  
F. Shanahan ◽  
M. A. Beaven
Keyword(s):  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Histamine Release ◽  
Immunoglobulin E ◽  
Calcium Ionophore ◽  
Ionophore A23187 ◽  
Con A ◽  
Kinase C ◽  
Mucosal Mast Cells

To study the control of histamine release, we developed techniques for culturing fundic mucosal mast cells. After enzyme dispersion, enrichment by elutriation, and overnight suspension culture, mast cells accounted for 30% of the cells present. Histamine release into the medium, measured by radioenzymatic assay, was stimulated by the lectin concanavalin A (Con A). Ragweed antigen released histamine in antisera-sensitized cultures. Con A-induced histamine release was enhanced by adenosine, but adenosine alone was inactive. The relative potency of adenosine analogues was consistent with interaction at an adenosine A1-receptor site. The calcium ionophore A23187 (0.1-1 microM) also induced histamine release. Phorbol esters that activate protein kinase C, such as phorbol 12-myristate 13-acetate, did not release histamine but enhanced release when added to low concentrations of A23187. In contrast, inactive phorbols, such as 4 alpha-phorbol 12,13-didecanoate, failed to enhance A23187-induced release. Parallel studies with canine hepatic mast cells yielded comparable results. We conclude that canine fundic mast cells possess receptors for immunoglobulin E and adenosine. Our data are consistent with increases in cytosolic calcium and protein kinase C activation working synergistically to stimulate fundic mast cells.

scholarly journals Protein kinase C regulates proliferation of mast cells and the expression of the mRNAs of fos and jun proto-oncogenes during activation by IgE-Ag or calcium ionophore A23187

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2354-2364
Author(s):  
D Baranes ◽  
E Razin
Keyword(s):  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Prolonged Treatment ◽  
Ionophore A23187 ◽  
Short Term ◽  
Kinase C ◽  
Short Term Exposure

Short-term stimulation (up to 16 hours) of interleukin-3 (IL-3)- dependent mouse bone marrow-derived mast cells, Abelson transformed mouse liver-derived mast cells, or rat basophilic leukemia cells by either IgE-Ag or calcium ionophore A23187 resulted in inhibition of their proliferation as measured by 3H-thymidine incorporation and MTT (tetrazolium) assays, and in accumulation of the mRNAs of c-fos, c-jun, junB and slightly of junD proto-oncogenes. The involvement of protein kinase C (PKC) in these responses was investigated by using several approaches of enzyme activity regulation. Direct activation of the PKC was achieved by short-term exposure of the cells to the PKC-specific activator phorbol 12-myristate-13-acetate (PMA). Inhibition of PKC activity was obtained by either prolonged treatment of the cells with PMA or by exposure of the cells to the PKC inhibitors H-7 and staurosporine. The results showed the following: (1) Short-term exposure of mast cells to PMA was sufficient to induce inhibition of proliferation. (2) An increase in PKC activity was associated with a decrease in the proliferation of IgE-dinitrophenol (DNP) or calcium ionophore A23187-stimulated cells. (3) A direct correlation was found between the increase in PKC activity and the increase in the level of the mRNAs of the jun proto-oncogenes in cells activated by both stimuli mentioned. (4) While an increase in PKC activity was associated with the upregulation of the level of c-fos mRNA during calcium ionophore A23187 stimulation, it showed the opposite effect on the expression of the mRNA of this proto-oncogene when the cells were triggered by IgE- DNP. Therefore, we concluded that PKC plays various roles in the expression of the mRNA of c-fos in activated mast cells depending on the stimulus involved. In addition, the expression of the mRNA of c-jun and junB proto-onogenes is not coordinately regulated with that of c- fos during immunologic stimulation. This discordancy, which is associated with the increase in PKC activity in mast cells, may play a role in the regulation of the transcription of AP-1-responsive genes, and therefore could be associated with the regulation of proliferation of these cells.

scholarly journals Protein kinase C regulates proliferation of mast cells and the expression of the mRNAs of fos and jun proto-oncogenes during activation by IgE-Ag or calcium ionophore A23187

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2354-2364 ◽  
Author(s):  
D Baranes ◽  
E Razin
Keyword(s):  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Prolonged Treatment ◽  
Ionophore A23187 ◽  
Short Term ◽  
Kinase C ◽  
Short Term Exposure

Abstract Short-term stimulation (up to 16 hours) of interleukin-3 (IL-3)- dependent mouse bone marrow-derived mast cells, Abelson transformed mouse liver-derived mast cells, or rat basophilic leukemia cells by either IgE-Ag or calcium ionophore A23187 resulted in inhibition of their proliferation as measured by 3H-thymidine incorporation and MTT (tetrazolium) assays, and in accumulation of the mRNAs of c-fos, c-jun, junB and slightly of junD proto-oncogenes. The involvement of protein kinase C (PKC) in these responses was investigated by using several approaches of enzyme activity regulation. Direct activation of the PKC was achieved by short-term exposure of the cells to the PKC-specific activator phorbol 12-myristate-13-acetate (PMA). Inhibition of PKC activity was obtained by either prolonged treatment of the cells with PMA or by exposure of the cells to the PKC inhibitors H-7 and staurosporine. The results showed the following: (1) Short-term exposure of mast cells to PMA was sufficient to induce inhibition of proliferation. (2) An increase in PKC activity was associated with a decrease in the proliferation of IgE-dinitrophenol (DNP) or calcium ionophore A23187-stimulated cells. (3) A direct correlation was found between the increase in PKC activity and the increase in the level of the mRNAs of the jun proto-oncogenes in cells activated by both stimuli mentioned. (4) While an increase in PKC activity was associated with the upregulation of the level of c-fos mRNA during calcium ionophore A23187 stimulation, it showed the opposite effect on the expression of the mRNA of this proto-oncogene when the cells were triggered by IgE- DNP. Therefore, we concluded that PKC plays various roles in the expression of the mRNA of c-fos in activated mast cells depending on the stimulus involved. In addition, the expression of the mRNA of c-jun and junB proto-onogenes is not coordinately regulated with that of c- fos during immunologic stimulation. This discordancy, which is associated with the increase in PKC activity in mast cells, may play a role in the regulation of the transcription of AP-1-responsive genes, and therefore could be associated with the regulation of proliferation of these cells.

Immunologic mast cell-mediated responses and histamine release are attenuated by heparin

1992 ◽  
Vol 73 (3) ◽  
pp. 1093-1101 ◽  
Author(s):  
J. Lucio ◽  
J. D'Brot ◽  
C. B. Guo ◽  
W. M. Abraham ◽  
L. M. Lichtenstein ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Immunoglobulin E ◽  
Specific Antigen ◽  
Calcium Ionophore ◽  
Intradermal Injection ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Dependent Manner

Heparin has been shown to act as a competitive inhibitor of inositol 1,4,5-triphosphate (InsP3) receptors in various cell types. Because InsP3 is one of the second messengers involved in stimulus-secretion coupling in mast cells, it is possible that heparin may inhibit mast cell-mediated reactions. Therefore, in allergic sheep, we tested this hypothesis in two mast cell-mediated reactions induced by immunologic and nonimmunologic stimuli: immediate cutaneous reaction (ICR) and acute bronchoconstrictor response (ABR). In 12 sheep allergic to Ascaris suum antigen, the surface area of the skin wheal was determined 20 min after intradermal injection (0.05 ml) of increasing concentrations of specific antigen, compound 48/80, and histamine, without and after pretreatment with heparin (100, 300, or 1,000 U/kg i.v.). Antigen, compound 48/80, and histamine produced concentration-dependent increases in ICR. Heparin “partially” inhibited the ICR to antigen and compound 48/80 in a dose-dependent manner without modifying the ICR to histamine. The heparin preservative benzyl alcohol was ineffective. In 11 additional sheep, specific lung resistance was measured before and after inhalation challenges with antigen, compound 48/80, and histamine without and with aerosol heparin pretreatment (1,000 U/kg). Heparin blocked the antigen- and compound 48/80-induced bronchoconstriction without modifying the airway effects of histamine. In isolated human uterine mast cells, heparin inhibited the anti-immunoglobulin E- but not the calcium ionophore- (A23187) induced histamine release. These data suggest that heparin inhibits the ICR and ABR induced by stimuli that produce immunologic and nonimmunologic mast cell degranulation without attenuating the effects of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals A role for protein kinase C in the membrane fusion necessary for platelet granule secretion

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2405-2413 ◽  
Author(s):  
JM Gerrard ◽  
LL Beattie ◽  
J Park ◽  
SJ Israels ◽  
A McNicol ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Membrane Fusion ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ultrastructural Changes ◽  
Ionophore A23187 ◽  
Kinase C ◽  
Granule Secretion ◽  
Dimethyl Amiloride

Abstract The addition of 1-oleoyl-2-acetylglycerol (OAG), or phorbol-12- myristate-13-acetate (PMA) to platelets induced the phosphorylation of a 47,000 dalton protein (47 Kd), fusion of granule membranes with membranes of the surface connected canalicular system, the formation of large vesicles and the secretion of serotonin. 1-(5- isoquinolinesulfonyl)-2-methyl-piperazine (H7), and sphingosine, inhibitors of protein kinase C, significantly inhibited the ultrastructural changes and the phosphorylation of 47 Kd. N-(2- guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), structurally similar to H7, but a weaker inhibitor of protein kinase C, did not attenuate these responses to OAG or to PMA. H7, but not HA1004, also markedly inhibited secretion induced by the synergistic combination of OAG and the calcium ionophore A23187. Amiloride and 5-(N,N dimethyl)- amiloride, inhibitors of the Na+/H+ transporter, did not inhibit the ultrastructural response and the protein phosphorylation induced by OAG, or the secretion induced by the combination of A23187 and OAG. The results link the activation of protein kinase C by diglycerides to the labilization and fusion of granule membranes important for secretion.

Protein kinase C activation and calcium mobilization decrease prolactin release from human decidual cells in early pregnancy

1993 ◽  
Vol 137 (2) ◽  
pp. 335-340 ◽  
Author(s):  
T. Kubota ◽  
S. Kamada ◽  
M. Taguchi ◽  
S. Sakamoto ◽  
T. Aso
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Early Pregnancy ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Calcium Mobilization ◽  
Ionophore A23187 ◽  
Prolactin Release ◽  
Kinase C ◽  
Decidual Cells

ABSTRACT The present study was undertaken to investigate the effects of protein kinase C (PKC) activation and calcium mobilization on the release of prolactin from human decidual cells in early pregnancy. Decidua obtained from patients in early pregnancy was enzymatically dispersed and cultured with phorbol myristate acetate (PMA) and calcium ionophore A23187 in a cell culture system. Prolactin in the medium was measured by enzyme-immunoassay. PMA, a PKC activator, dose-dependently attenuated the release of prolactin from cultured decidual cells, while a PKC inhibitor, H7, significantly (P < 0·001) diminished the effect of PMA on prolactin release. PMA had no effect on cell numbers or DNA synthesis in the decidual cells during culture. It did not significantly increase the generation of inositol phosphate in decidual cells prelabelled with myo[3H]inositol and it had no effect on intracellular calcium concentration ([Ca2 + ]i). Calcium ionophore A23187, a Ca2 +-mobilizing agent, also significantly (P<0·001) attenuated the release of prolactin and potentiated the PMA-induced suppression of prolactin release from decidual cells. These findings suggest that activation of PKC and mobilization of Ca2+ may be involved in regulating prolactin release from human decidual cells. The PMA-induced suppression of prolactin release is not triggered by phosphoinositide hydrolysis nor by the increase in [Ca2 + ]i in decidual cells. Journal of Endocrinology (1993) 137, 335–340

Influence of protein kinase C, cAMP and phosphatase activity on histamine release produced by compound 48/80 and sodium fluoride on rat mast cells

1992 ◽  
Vol 37 (1-2) ◽  
pp. 1-7 ◽  
Author(s):  
L. M. Botana ◽  
A. Alfonso ◽  
M. A. Botana ◽  
M. R. Vieytes ◽  
M. C. Louzao ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Histamine Release ◽  
Phosphatase Activity ◽  
Sodium Fluoride ◽  
Kinase C ◽  
Rat Mast Cells

scholarly journals Synergistic signals in the mechanism of antigen-induced exocytosis in 2H3 cells: evidence for an unidentified signal required for histamine release.

1987 ◽  
Vol 105 (3) ◽  
pp. 1129-1136 ◽  
Author(s):  
M A Beaven ◽  
D F Guthrie ◽  
J P Moore ◽  
G A Smith ◽  
T R Hesketh ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Histamine Release ◽  
Phorbol Ester ◽  
Inositol Phosphates ◽  
Synergistic Action ◽  
Ionophore A23187 ◽  
Kinase C

The aim of this study was to determine whether the increase in cytosolic free Ca2+ concentration ([Ca2+]i) in response to antigen (aggregated ovalbumin) on IgE-primed 2H3 cells was sufficient to account for exocytosis. When the [Ca2+]i responses to antigen and the Ca2+ ionophore A23187 were compared, A23187 was much less effective at releasing histamine at equivalent [Ca2+]i increases, and little or no stimulated histamine release occurred with A23187 concentrations that matched the [Ca2+]i response to antigen concentrations that stimulated maximal histamine release. The [Ca2+]i response to antigen is not, therefore, sufficient to account for exocytosis, although extracellular Ca2+ is necessary to initiate both the [Ca2+]i response and histamine release: the antigen must generate an additional, unidentified, signal that is required for exocytosis. To determine whether this signal was the activation of protein kinase C, the effects of the phorbol ester 12-0-tetradecanoyl phorbol 13-acetate (TPA) on the responses to antigen were examined. TPA blocked the antigen-induced [Ca2+]i response and the release of inositol phosphates but had little effect on histamine release and did not stimulate exocytosis by itself. The unidentified signal from the antigen is therefore distinct from the activation of protein kinase C and is generated independently of the [Ca2+]i response or the release of inositol phosphates. Taken together with other data that imply that there is very little activation of protein kinase C by antigen when the rate of histamine release is maximal, it is concluded that the normal exocytotic response to antigen requires the synergistic action of the [Ca2+]i signal together with an unidentified signal that is not mediated by protein kinase C.

scholarly journals Rapid expression of protooncogenes c-fos and c-myc in B-chronic lymphocytic leukemia cells during differentiation induced by phorbol ester and calcium ionophore

Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1656-1663 ◽  
Author(s):  
HG Drexler ◽  
JW Janssen ◽  
MK Brenner ◽  
AV Hoffbrand ◽  
CR Bartram
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Chronic Lymphocytic Leukemia ◽  
Phorbol Ester ◽  
Messenger Rna ◽  
Calcium Ionophore ◽  
Lymphocytic Leukemia ◽  
Calcium Flux ◽  
Ionophore A23187 ◽  
Kinase C

Abstract The peripheral blood mononuclear cells from patients with B-chronic lymphocytic leukemia (B-CLL) were incubated for 0.5 h to 72 h in the presence of the phorbol ester TPA, the calcium ionophore A23187, or a combination of these reagents. Using Northern blot analysis, total cellular RNA was prepared from cells harvested at different time points and hybridized with DNA clones specific for the protooncogenes c-fos and c-myc. While untreated control cells lacked detectable amounts of messenger RNA (mRNA), increase in the level of c-fos mRNA was noted as early as 0.5 h after exposure to the inducers. Peaks of c-fos and c-myc transcript accumulation were seen at 1 h and 4 h after induction, respectively. The most effective inducer was double stimulation with TPA plus A23187. The kinetics of c-fos and c-myc mRNA accumulation in B- CLL appear to be similar to those reported for normal lymphocytes that have been either activated by physiologic external stimuli or by direct activators of protein kinase C and calcium flux (such as TPA and A23187). No direct link between oncogene expression and proliferation or differentiation parameters could be established. These results document that expression of c-fos and c-myc genes, which are among the earliest events following stimulation of the protein kinase signal transduction pathway, can be successfully induced in B-CLL cells. The data provide further evidence for the hypothesis that signal transmission downstream of protein kinase C is intact in B-CLL.

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