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PubMed · 1517003

Basophil degranulation control.

B Hadjaj·Y Cherruault·J Sainte Laudy
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Abstract

We first present a global simulation model describing inhibition of human basophil degranulation by means of high dilutions. Then we study an optimal control problem associated to a non-linear compartmental model. This control is associated to an antigen concentration. For solving this control problem we used a dynamic programming method.

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Basophil Degranulation TestComputer SimulationHumansQuality ControlComparative StudyJournal Article

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BibTeXRIS

B Hadjaj, Y Cherruault, J Sainte Laudy. 1992. Basophil degranulation control.. https://doi.org/10.1016/0020-7101(92)90065-z

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PubMed2006

Initial Fc epsilon RI-mediated signal strength plays a key role in regulating basophil signaling and deactivation.

BACKGROUND: Mediator releases after high-affinity IgE receptor (Fc(epsilon)RI) cross-linking in basophils and mast cells crucially govern the symptoms of allergic disease and amplify underlying T(H)2-type responses. Interestingly, the dose-response curve for Fc(epsilon)RI activation is bell-shaped, with supraoptimal stimulation leading to reduced mediator release. OBJECTIVE: We sought to characterize the mechanisms responsible for this control of Fc(epsilon)RI-triggered basophil activation. METHODS: Human basophils were purified by means of Ficoll density centrifugation, elutriation, and negative selection with immunomagnetic beads. Various intracellular signal protein activities were assessed by means of Western blotting, and mediator releases were analyzed either spectrofluorometrically (histamine) or by means of ELISA (IL-4 and IL-13). RESULTS: Supraoptimal anti-IgE concentrations led to lower mediator release than optimal concentrations but simultaneously to considerably faster histamine release kinetics. In parallel, basophil signaling proteins (Syk, p38 mitogen-activated protein kinase, and extracellular signal-regulated kinases 1 and 2) were more rapidly phosphorylated at higher anti-IgE concentrations but more transiently activated in the supraoptimal range. This endogenous regulation most likely involved src homology 2 domain-containing inositol 5' phosphatase (SHIP), which was highly phosphorylated after supraoptimal anti-IgE triggering compared with lower stimulus concentrations. Conversely, N-formyl-methionyl-leucyl-phenylalanine-stimulated basophils failed to phosphorylate SHIP in the supraoptimal concentration range and did not display a bell-shaped dose-response curve. CONCLUSION: The kinetics of IgE-mediated signaling and mediator release in primary human Fc(epsilon)RI(+) cells varies substantially according to the magnitude of stimulation, and SHIP most likely plays an important role in terminating these events. CLINICAL IMPLICATIONS: The speed of allergic symptom generation depends on the degree of IgE receptor triggering, which is downregulated by SHIP, a potential target for allergy therapy.

Basophil Degranulation Test↗
PubMed2005

Replication study concerning the effects of homeopathic dilutions of histamine on human basophil degranulation in vitro.

BACKGROUND: Various investigators have observed significant effects of highly diluted histamine on human basophil degranulation in vitro, compared to corresponding water controls. However, active and inactive dilution levels differed in most studies. OBJECTIVE: We aimed to reproduce former studies with flow-cytometry using rigorously controlled experimental conditions to minimise confounding factors. METHODS: In seven independent experiments, basophils of the same human donor were incubated with diluted histamine (up to 10(-34)M) or water controls and activated with anti-IgE antibodies. Basophil activation was determined by using bi-colour flow-cytometry. Experiments were blinded and performed with a randomised arrangement of the solutions on microtiter-plates. RESULTS: Histamine at the dilutions 10(-2)M and 10(-22)M was associated with a significant inhibition of basophil degranulation (p=0.018, Wilcoxon signed rank test) of 23.1% and 5.7%, respectively, if compared to "diluted" water treated in an identical manner. However, if all controls were pooled, only histamine 10(-2)M had a significant effect. Significant effects were seen for row numbers of the microtiter plates. CONCLUSION: We were not able to confirm the previously reported large effects of homeopathic histamine dilutions on basophil function of the examined donor. Seemingly, minor variables of the experimental set up can lead to significant differences of the results if not properly controlled.

Basophil Degranulation Test↗
PubMed2003

[Basophil activation test in the diagnosis of allergy to medicines].

In this paper we study the reliability of the basophil activation test (BAT) in the "in-vitro" diagnosis of allergy to betalactams and to metamizol, and the sensitivity and specificity of the technique are analyzed. To this end, we studied 58 patients allergic to betalactam antibiotics with a positive cutaneous test facing any derivative of penicillin and 30 healthy controls who tolerated betalactams, and 26 patients allergic to metamizol with an immediate reaction and 30 healthy controls who tolerated the medicine. Sensitivity to BAT in allergy to betalactams was 52.8%, and specificity was 92.6%. For metamizol, sensitivity was 42.3% and specificity was 100%. The positive predictive value of BAT in allergy to betalactams was 18.9% and the negative predictive value was 98.4%. For metamizol, the positive predictive value of the technique was 100% and the negative predictive value was 99.4%. The joint use of BAT and CAP (specific IgE) makes it possible to diagnose some 65% of patients allergic to betalactams. The combined use of cutaneous tests and BAT in allergy to metamizol detects 70% of the cases. BAT is a useful, non-invasive technique in the "in-vitro" diagnosis of allergy to betalactams and metamizol.

Basophil Degranulation Test↗