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C Burtin

Publications and source records attributed to C Burtin.

At least 19 recordsLinked to original sources
PubMed1995

Voltage-dependent ion channels on human basophils: do they exist?

The presence of voltage-dependent ion channels (particularly Ca2+ channels) on the surface of 'non excitable' cells such as human basophils is a matter of debate. Indeed, in basophils, Ca2+ entry or mobilization is not sufficient by itself to trigger secretion, although enhanced cytosolic Ca2+ concentration increases it. In order to address this question, we used a two-signal model and we report here experiments which suggest the presence of voltage-dependent structures directly or indirectly linked to membrane Ca2+ pathways. Indeed, it is known that, in the presence of PMA at threshold concentration (1st signal), elevation of cytosolic Ca2+ (2nd signal) induces histamine release. We observed that a depolarizing external solution (high K+) induced a Ca(2+)-dependent release of histamine from PMA-treated human basophils. High K+ alone did not induce histamine release. Although the voltage-sensitive component and the physiological relevance of this mechanism remain to be defined, these results suggest that this voltage-dependent Ca2+ influx in the human basophil could contribute to the up-regulation of histamine release.

Basophils↗
PubMed1994

Regulation of human basophil activation; the role of Na+ and Ca2+ in IL-3-induced potentiation of IgE-mediated histamine release from human basophils.

The release of mediators from human basophils is strongly enhanced by IL-3. However, the signalling pathways of IL-3 are poorly defined in these cells. Since external Ca2+ and Na+ play important regulating roles in histamine release, the possibility that these cations could be involved in the potentiation by IL-3 of the anti-IgE-induced histamine release from human basophils was considered, and it was observed that: (i) IL-3 dramatically decreased the external Ca2+ requirement for IgE-mediated histamine release. However, histamine release from IL-3-treated basophils became only partially independent of external Ca2+, since addition of EGTA in the external medium abolished the effect of IL-3; (ii) decreasing Na+ influx by lowering external Na+ concentration in isosmotic medium inhibited the potentiating effect of IL-3 on IgE-mediated release; (iii) amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exchanges, and its derivative, benzamil, more specific for Na+/Ca2+ exchanges, inhibited the release potentiated by IL-3. In contrast, the amiloride derivative 5-(N,N-dimethyl)-amiloride, more specific for Na+/H+ exchanges, slightly increased the IL-3-enhanced release. Thus, the decreased requirement for external Ca2+ and the dependence on external Na+, taken with the effect of the Na+/Ca2+ exchange inhibitors, suggest that Na+/Ca2+ exchanges are involved in the IL-3-induced enhancement of IgE-mediated human basophil histamine release.

Amiloride↗
PubMed1992

Regulation of human basophil activation. II. Histamine release is potentiated by K+ efflux and inhibited by Na+ influx.

Na+ and K+ are the major extra- and intracellular cations, respectively. We have thus studied the role of these ions on human basophil histamine release by modifying their transmembrane gradients or by increasing membrane ion fluxes using ionophores. 1) When external Na+ (reduced to 4 mM) was replaced by the nonpermeating Na+ substitute N-methyl-D-glucamine, the release of histamine was enhanced in 2 mM Ca2+ (from 37.5 +/- 8.0% in 140 mM Na+ to 68.5 +/- 9.1% in low Na+) and became possible in the presence of low Ca2+ (at 1 microM Ca2+: from 0.6 +/- 0.7% in 140 mM Na+ to 36.2 +/- 8.0% in low Na+); moreover, in low Na+, the release of histamine became partly independent on Ca2+ influx. 2) Increasing the Na+ influx with the cation channel-forming gramicidin D inhibited the release of histamine by 33.2 +/- 13.6% (n = 6) in an external Na(+)-dependent manner. 3) Decreasing K+ efflux using K+ channel blockers (4-aminopyridine, quinine, sparteine) inhibited histamine release in a dose-response manner. 4) The K+ ionophore valinomycin, which increases K+ efflux, slightly enhanced IgE-mediated histamine release when used alone, whereas it potentiated the release of histamine from leukocytes previously treated with 4-aminopyridine by 57.0 +/- 18.6% (n = 7). 5) Decreasing K+ efflux by increasing external K+ inhibited IgE-mediated release in a similar manner as Na+ did. The inhibitory effects of Na+ and high K+ were not additive, thus suggesting that both cations inhibited the release by a common mechanism. In conclusion 1) our data evidence that histamine release from human basophils is inhibited by Na+ influx and potentiated by K+ efflux; 2) they suggest that K+ channels are present on the basophil membrane and that Na+ and K+ fluxes act on histamine release most probably via modulation of membrane potential.

4-Aminopyridine↗
PubMed1992

Modifications in tissue histamine levels in mice treated with chronic epicutaneous application of phorbol-12-myristate-13-acetate.

Chronic epicutaneous application of phorbol-12-myristate-13-acetate (PMA) on the right flank of C 57 BL/6 mice induces an inflammatory reaction and a selective increase in skin histamine level at the site of treatment. Tissue histamine levels were not increased at other sites such as contralateral skin, stomach rumen and skeletal muscle, and were decreased in stomach fundus and dorsal skin. These results are in agreement with the hypothesis that mast cells play a significant role in cutaneous inflammation induced by PMA.

Administration, Cutaneous↗
PubMed1992

Regulation of human basophil activation. III. Impairment of the inhibitory effect of Na+ on IgE-mediated histamine release in patients with allergic rhinitis.

We recently observed that external Na+ inhibited the IgE-dependent human basophil histamine release (HR) in normal subjects. In this article we report differences in the Na+ effect on basophil HR between normal subjects (n = 16) and age matched patients with allergic rhinitis (AR) (n = 18). As expected, in vitro anti-IgE-stimulated basophils from the group with AR released greater amounts of histamine than basophils from the normal group. However, removal of external Na+ (and replacement by N-methyl-D-glucamine) abolished this difference between the two groups. HR in the normal group increased to the same high level as that of the group with AR. By contrast, the release of histamine in the group with AR was not further increased by Na+ removal. Although high releasers were more frequent in the group with AR, the absence of effect after Na+ removal was not due to the high basal release level (in the presence of Na+) because no effect after Na+ removal was also observed with medium releasers. These results strongly suggest that increased basophil HR in populations with AR, and possibly in other allergic populations, is linked to a defect in the inhibitory effect of Na+.

Adult↗
PubMed1992

Regulation of human basophil activation. IV. Dissociation between cationic dye binding and histamine release: role of Ca2+ ions.

In previous studies we observed that in vitro histamine release from human basophils could be dissociated from the loss of affinity of basophil granules for a cationic dye, toluidine blue. In the present study we further explored the intracellular signals leading to the decrease in toluidine blue positive basophil (TB+) numbers, with or without histamine release. Since Ca2+ mobilization is a crucial event in secretion and particularly in histamine release, we studied the role of Ca2+ in histamine release as compared to TB+ decrease. In the presence of external Ca2+ (2 mM): i) Ca2+ channel antagonists verapamil and nifedipine up to 10 microM were without effect on IgE-mediated histamine release and TB+ decrease; ii) loading of the leucocytes with Quin2 or preincubation with TMP-8, an internal Ca2+ antagonist, significantly inhibited the release of histamine and the decrease of TB+ basophils. In the absence of added external Ca2+:i) histamine release was abolished whereas the decrease of TB+ was not modified, even in the presence of EGTA;ii) the decrease of TB+ could be inhibited by prolonged EGTA preincubation, by Quin2 loading and incubation with TMB-8. We conclude that histamine release requires both external Ca2+ influx and mobilization of internal Ca2+. In contrast, no influx of external Ca2+ is required for TB+ decrease in which, however, internal Ca2+ mobilization appears to play an important role.

Antibodies, Anti-Idiotypic↗
PubMed1991

Regulation of human basophil activation. I. Dissociation of cationic dye binding from histamine release in activated human basophils.

Human basophil activation was demonstrated by histamine release (HR) and by the decrease of the toluidine blue-positive basophils (TB+). In four experimental systems, TB+ number decreased in the absence of HR (1) in basophils from atopic subjects stimulated by allergen concentrations below the threshold for HR, (2) in basophils sensitized by anti-2,4-dinitrophenyl IgE stimulated by noncovalently linked 2,4-dinitrobenzene sulfonic acid-human serum albumin (also, the threshold for decrease of TB+ required lower concentrations of sensitizing anti-2,4-dinitrophenyl IgE than for HR), (3) in low Ca++ medium, and (4) in the presence of the Na+/H+ exchanger, monensin. These results suggest that (1) there is a lower threshold for TB+ decrease than for HR in allergen concentration, number of membrane IgE molecules, and number of IgE cross-linkings; moreover, external Ca++ requirement is lower for decrease of TB+ than for HR and (2) TB+ decrease reflects either granule exocytosis or, in the absence of HR, biochemical changes (most probably cation exchanges) altering the interaction of the basic dye with the granules. Thus, monitoring decrease in TB+ allows detection of basophil activation in the absence of HR.

Basophils↗
PubMed1990

Bimodal IgG4-mediated human basophil activation. Role of eosinophils.

The role of IgG4 antibodies in allergic disorders is suspected. Yet, their presence on human basophil membrane has not been demonstrated and the mechanism of the degranulation induced by anti-IgG4 antibodies remains unclear. As previously reported, we observed that monoclonal anti-IgG4 (10 to 100 micrograms/ml) induced histamine release in the presence of D2O from leukocytes of normal and atopic subjects. The release was accompanied by a decrease of the number of toluidine blue-positive basophils (TB+). Histamine release and TB+ decrease were also observed with lower concentrations of anti-IgG4 (1 to 100 pg/ml). Since basophil activation assessed by TB+ decrease was more sensitive than histamine release, we thus used the former method to further study the mechanisms of the anti-IgG4- vs anti-IgE-induced basophil activation. Basophil activation by anti-IgG4 at 1 to 100 pg/ml, but not by anti-IgG4 at 10 to 100 micrograms/ml or anti-IgE, required the presence of polymorphonuclear cells. Furthermore, anti-IgG4-stimulated purified eosinophils, but not neutrophils, released basophil-activating factors identified as cationic proteins from eosinophils. Thus, the human basophil can be activated by anti-IgG4 via two different mechanisms according to the antibody concentration. At high concentrations (10 to 100 micrograms/ml) basophil activation does not require the presence of polymorphonuclear cells whereas at lower concentrations (1 to 100 pg/ml) the presence of eosinophils is necessary. We propose that in the latter concentration range, basophil activation is a two-step process: 1) release by anti-IgG4 of eosinophil cationic proteins that 2) will, in turn, activate human basophils. This study lends support to the role of IgG4 and eosinophils in anaphylactic reactions.

Antibodies, Anti-Idiotypic↗
PubMed1990

Monoclonal IgE-mediated cardiac hypersensitivity reactions in the guinea-pig.

Isolated heart preparations were prepared from guinea-pigs passively sensitized with mouse anti-DNP monoclonal IgE to study hemodynamic parameters and histamine release upon antigen challenge (DNP-BSA). In the best experimental conditions a triphasic response (increase, decrease, increase) in heart rate and in coronary flow occurred during 10 minutes after challenge. Coronary flow dramatically decreased (50%) at 2.5 min flanked by two periods of increase in flow and tachycardia (+ 55% of the basal heart rate). Contractile force decreased and remained at 80% of its initial value. Histamine is released within 2 minutes after antigen injection. After this period, the observed hemodynamic modifications seem to be due to other anaphylactic mediators such as prostaglandins, leukotrienes and most probably paf-acether.

Animals↗
PubMed1990

Blood histamine levels in HIV-1-infected infants and children.

Blood histamine levels (BHL; ng histamine base/ml blood, mean +/- SEM) were determined in 118 infants born to HIV-1-infected mothers and in children infected after blood transfusion. In asymptomatic infected infants, BHL were not significantly different from HIV-1-negative infants born to HIV-infected mothers (54.1 +/- 5.6 vs. 56.4 +/- 3.5). BHL progressively decreased in the group with polyadenopathies (40.0 +/- 4.0), in the group with AIDS-related complex (28.8 +/- 2.9), and in patients with AIDS (20.4 +/- 0.9). The decrease in BHL was associated with a decrease in blood basophil number.

Child↗
PubMed1989

Comparison between number of basophils, blood histamine, and histamine release in cancer and noncancer patients.

In cancer patients with primary tumor with or without metastasis or metastasis alone, by comparison with healthy subjects and noncancer patients, the decrease in blood histamine levels is due to a decrease in total basophil number. These basophils have a normal content of histamine (1 to 2 pg per basophil) and are able to release histamine. The percentage of anti IgE-induced histamine release is not significantly different than in noncancer patients. The scarcity of basophils in cancer patients is not due to a leukopenia. Blood histamine levels and total basophil number are normal in patients after successful excision of their primary tumor without metastasis.

Adult↗
PubMed1988

Biochemical and morphological modifications in dexamethasone-treated mouse bone marrow-derived mast cells.

Addition of 1 microM dexamethasone (DM) to bone marrow-derived mast cells (BMMC) induced a time-dependent increase in cell histamine content. The latter reached a plateau of 2.5 micrograms/1 x 10(6) cells after 11 days in culture, compared with 100 ng/1 x 10(6) for untreated BMMC. Steroids, such as beta-estradiol, androsterone, and testosterone (1 microM), did not alter the histamine content of BMMC, whereas progesterone (1 microM) induced a moderate increase. Other glucocorticosteroids also enhanced histamine content, suggesting that the observed increase was specific for glucocorticosteroid. Treatment of BMMC with 1 microM DM for 14 days inhibited the Ag-induced, IgE-mediated release of histamine, beta-hexosaminidase, platelet-activating factor-acether, LTB4, and LTC4 by 65 +/- 3%, 66 +/- 1%, 93 +/- 3%, 66 +/- 2%, and 74 +/- 10%, respectively (mean +/- 1 SD, n = 3). In contrast with untreated cells which produce less than 2 ng/1 x 10(6) cells PGD2 after Ag challenge, DM-treated BMMC generated 16.8 +/- 0.3 ng/1 x 10(6) cells PGD2. Moreover, most of DM-treated BMMC became Alcian blue+/safranin+ and by ultrastructure, exhibited numerous cytoplasmic granules filled with abundant and uniform electron-dense matrix. The present results indicate that DM-treated BMMC exhibit biochemical and functional properties different from immature untreated cells, suggesting that a maturation-like process occurred in vitro during DM treatment.

Alcian Blue↗
PubMed1988

Study of histamine release induced by acute administration of antitumor agents in dogs.

The effects of eight antitumoral drugs known to cause anaphylactoid side effects in clinical use were studied in dogs. Blood pressure, heart rate, and blood and plasma histamine levels were monitored. L-asparaginase, methotrexate, 5-fluorouracil, bleomycin, and cisplatin had no effect on these parameters. Doxorubicin, Vehem (teniposide), and Vepeside (etoposide) induced hypotension, tachycardia, and a rise in histamine levels. In the cases of Vehem and Vepeside, the excipient (respectively, cremophor EL and tween 80) induced the same effects. These agents, like elliptinium, which had been previously studied, induce nonspecific histamine release--unlike the other drugs studied. The mechanism of clinically observed anaphylactoid side effects is discussed in the light of these findings.

Anaphylaxis↗
PubMed1988

Inhibitory effect of oral cetirizine on in vivo antigen-induced histamine and PAF-acether release and eosinophil recruitment in human skin.

The use of a noninvasive skin chamber technique in vivo in pollen-sensitive patients allowed us to quantify the time-course release of histamine and the recruitment of inflammatory cells (i.e., neutrophils, monocytes, and eosinophils) in skin sites challenged with pollen, histamine, and compound 48/80. The new H1-receptor antagonist, cetirizine 2 HCl, orally administered with 10 mg once a day to pollen-sensitive patients in a double-blind, crossover study versus placebo, induced a significant decrease in the wheal-and-flare cutaneous reaction induced by intradermal injection of pollen, histamine, and compound 48/80. It also significantly inhibited the immediate histamine release occurring in skin chambers after pollen introduction, whereas it did not significantly inhibit the late release. In patients receiving placebo, we detected platelet-activating factor-acether in media collected at the sixth hour from chambers filled with pollen. With cetirizine 2 HCl treatment, platelet-activating factor-acether was not detected in chamber media. Interestingly, cetirizine 2 HCl significantly reduced the eosinophil recruitment observed on the superficial dermis 24 hours after pollen challenge.

Administration, Oral↗
PubMed1988

Clinical improvement in advanced cancer disease after treatment combining histamine and H2-antihistaminics (ranitidine or cimetidine).

In a randomized study 31 patients with advanced cancer disease in whom classical anticancer therapy had been abandoned received a daily combination of subcutaneous histamine and oral H2-antihistaminics. In 27 patients, treatment induced a marked clinical improvement as shown by a large rise in performance status (Karnofsky scale). Ten patients were still alive 3-14 months after initiation of treatment. Average survival in the 31 treated patients (172 +/- 113 days) was significantly longer than in 34 non-treated patients with similar advanced cancer (26 +/- 16 days, P less than 0.00001). In six treated patients, the size of liver and lung metastases decreased. Histamine was perfectly tolerated up to 4 mg/day.

Adult↗
PubMed1988

Prostaglandin D2 generation in mouse bone marrow-derived mast cells exposed to dexamethasone is associated with endogenous peroxidase activity.

The appearance of fixative-sensitive peroxidase activity in the nuclear envelope and endoplasmic reticulum of bone marrow-derived mast cells (BMMC) cultured in the presence of 1 microM dexamethasone (DM) for up to 14 days and its relationship with immunologic release of prostaglandin D2 (PGD2) by these cells were studied. Endogenous peroxidase activity, previously shown as a marker of arachidonic acid metabolism in various cell types, was visualized by cell incubation in 3,3' diaminobenzidine-containing solution before glutaraldehyde fixation. PGD2 release was induced by passive sensitization of BMMC with an optimal dose of monoclonal IgE and subsequent challenge with specific a antigen. We found that 4-week-old BMMC, used as the starting population of the present study, exhibited immature morphologic features, did not present peroxidase activity when cytochemically processed, and released minute amounts of PGD2 in response to IgE-dependent stimulation. When such BMMC were exposed to DM during 24 hours, they showed aldehyde-inhibited peroxidase activity in the perinuclear envelope and a few endoplasmic reticulum segments. As compared with untreated cells, 24-hour DM-exposed BMMC released higher amounts of PGD2 upon immunologic stimulation. After an additional 14-day period of DM exposure, an intense peroxidase activity was detected in the perinuclear envelope and the endoplasmic reticulum of BMMC, which, under immunologic stimulation, released as much as 42.4 +/- 14.7 ng of PGD2/1 x 10(6) cells. Aminotriazole (20 and 50 mM) extinguished both peroxidase activity and PGD2 release from BMMC whereas indomethacin (1 microM) suppressed PGD2 production, but did not alter endogenous peroxidase activity. Previous cell fixation with glutaraldehyde totally inhibited endogenous peroxidase reaction in DM-exposed BMMC. Moreover, 14-day DM-exposed BMMC exhibited morphologic characteristics of mature mast cells and possessed alcian blue+/safranin+ granules. Therefore, the present data suggest that appearance of peroxidase activity in the nuclear envelope and the endoplasmic reticulum of DM-exposed BMMC is associated with the ability of the cells to synthetize PGD2 and appears as a cytochemical marker of the in vitro maturation of mouse bone marrow-derived mast cells.

Aldehydes↗