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ABSTRACT: We have studied the effect of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)), two reactive oxygen species (ROS) on histamine release (HR) from RBL-2H3 cells, a rat mucosal-type mast cell line. Marked HR was elicited by antigen (DNP-HSA), calcium ionophore A23187, sodium fluoride or phospholipase C, but not with compound 48/80 or 1,2-dioctanoyl-sn-glycerol. The NO-synthase substrate L-arginine and its inactive enantiomer (D-arginine), each on its own, induced a small but significant increase in HR above the basal level. However, the NO-donors (sodium nitroprusside or NaNO(3)) or the NO-synthase inducer lipopolysaccharide did not induce HR. Moreover, methylene blue (MB), which inhibits guanylate cyclase and N(omega)-nitro-L-arginine (L-NA), an inhibitor of NO synthase, were also without effect on either the basal HR or the L-arginine-induced HR. HR induced by A23187, DNP-HSA, sodium fluoride or phospholipase C was markedly reduced by MB, but mildly by L-NA (both at 1-100 microM). H(2)O(2) (0.01-1.0 mM) on its own did not induce HR, but it had a potent inhibitory effect on DNP-HSA- or A23187-induced HR, which was not reversed by L-NA (1-100 microM). Taken together, it seems that neither the stimulatory nor the inhibitory effects of the NO-related compounds on HR can be attributed to NO, but rather to other mechanisms. The inhibition of HR by H(2)O(2) also does not involve NO and suggests a negative feedback regulatory role for the peroxide in the allergic inflammation.
Biochemical Pharmacology 01/2002; 62(11):1537-44. · 4.70 Impact Factor
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Inflammation Research 05/2001; 50 Suppl 2:S118-9. · 2.11 Impact Factor
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ABSTRACT: Using the ratiometric Ca2+ indicator, indo-1, the antigen-induced increase in intracellular Ca2+ concentration ([Ca2+]i) was measured in individual RBL-2H3 cells which had been passively sensitized with monoclonal antibody to the dintrophenyl (DNP) haptenic group. Antigenic stimulation using DNP-human serum albumin conjugate (DNP-HSA) induced concentration-dependent asynchronous Ca2+ oscillations, or irregular spikes. To achieve a quantitative comparison of the effects of different concentrations of antigen on changes in Ca2+[i, the area under the curve (AUC) of Ca2+ oscillations in each cell was calculated. The dose-response curve of the calculated AUC is consistent with the bell-shaped dose-response curve for antigen-induced mediator release, depolarization and 86Rb(+)-efflux. Ca2+ oscillations induced by antigenic stimulation were abolished by removal of external Ca2+ and the subsequent reintroduction of external Ca2+ caused their resumption. To investigate the role of Ca2+ oscillations in the secretory response, changes in [Ca2+]i induced by concanavalin A (Con-A), A23187, thapsigargin and NECA were also monitored. Con-A mimicked the response induced by antigen, whilst A23187 and thapsigargin induced a large transient non-oscillatory response. NECA, an adenosine receptor agonist, induced only a small transient rise in Ca2+[i without oscillatory behaviour. Since all these stimuli accept NECA-induced degranulation in these cells, it is suggested that, although Ca2+ oscillations are not essential for the initiation of secretion, they probably underlie the in-vivo physiological response of mast cells and basophils to an antigenic challenge. They also seem to enhance the efficacy of the Ca2+ signal.
Cell Calcium 01/2000; 26(6):261-9. · 3.77 Impact Factor
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Inflammation Research 04/1996; 45 Suppl 1:S7-8. · 2.11 Impact Factor
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Inflammation Research 05/1995; 44 Suppl 1:S7-9. · 2.11 Impact Factor
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Inflammation Research 05/1995; 44 Suppl 1:S10-1. · 2.11 Impact Factor
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ABSTRACT: In patients with anaphylactoid reactions (AR) to neuromuscular blocking drugs (NMB), eosinophil cationic protein (ECP) was released both in vivo and in vitro, and in IgE-dependent and IgE-independent reactions. Thus, eosinophils may play a role in both types of reactions, and ECP release tests may be of value in the diagnosis and study of the mechanism of AR.
Agents and Actions 07/1994; 41 Spec No:C11-3.
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ABSTRACT: Binding-inhibition studies involving human IgE antibody to suxamethonium, SUX (from a patient with a near-fatal reaction), were performed with five different quaternary ammonium compounds (QAC): three common ingredients of cosmetics and two commonly used disinfectants, cetrimide and benzalkonium. All the five QAC showed immunological cross-reaction with SUX. In addition, at high concentrations, they released histamine from basophils of normal subjects. Thus, QAC may be both sensitizers and histamine releasers.
Agents and Actions 07/1994; 41 Spec No:C138-9.
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ABSTRACT: Several aspects of in vitro tests for life-threatening anaphylactoid reactions (AR) to neuromuscular blockers (NMB, muscle relaxants) were addressed and highlighted. They include topics which have been under study in our centre in the past few years. Already available tests and newly developed ones were assessed for diagnostic and predictive value, as well as for usefulness in understanding of mechanism(s) of AR. The theoretical and practical aspects of radioallergosorbent tests (RAST) for antibodies to NMB (particularly IgE), their predictive value and their possible use in "screening" with the hope of preventing AR are discussed. Confirmatory tests after AR include plasma or serum histamine/methylhistamine, tryptase and possibly eosinophil cationic protein (ECP), all of which point to activation of mast cells, basophils, eosinophils and possibly other inflammatory cells. Future anesthetics after AR can be guided by measurement of the in vitro release of histamine, leukotrienes and possibly eosinophil cationic protein (ECP) and serum antibodies. Antibody studies (mainly IgE by RAST) are valuable for diagnosis and, together with other tests, can throw light on cross-reaction and further clarify the mechanisms of AR. In RAST (IgE)-negative cases of AR, which may be due to immune or nonimmune mechanisms, mediator release measurements are particularly useful. Lymphocyte stimulation tests may also be useful in such cases. RASTs cannot be advocated for general preoperative screening, as yet. Further development or selection of potentially "susceptible" subpopulations may improve the predictive value of these tests.
Annales Françaises d Anesthésie et de Réanimation 02/1993; 12(2):203-11. · 0.84 Impact Factor
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ABSTRACT: This chapter will first briefly deal with some of the controversial issues surrounding allergic reactions to anaesthetics. Other points which appear to be of fundamental importance and which need further investigation will also be mentioned. Readers are referred to other chapters for further information on some of the issues.
Monographs in allergy 02/1992; 30:1-14.
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Monographs in allergy 02/1992; 30:24-53.
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ABSTRACT: The majority of patients with anaphylactoid reactions (AR) under general anaesthesia showed histamine release from basophil leucocytes (HRL) by neuromuscular blockers in vitro (none in normals) and high levels of serum IgE antibody (detected by the 'new' paper radioallergosorbent test, RAST; little or none in normals) which reacted with the quaternary ammonium group of choline, and less frequently of alcuronium, strongly suggesting that IgE antibody, HRL and AR are related. Skin tests on their own are of limited value.
Agents and Actions 06/1991; 33(1-2):208-11.
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ABSTRACT: Compound 48/80-induced histamine release (HR) from the isolated perfused rat heart was markedly and significantly inhibited by picumast (PIC), possibly by acting as a calmodulin antagonist (CMA) or membrane stabilizer. Trifluoperazine (TFP, another CMA in clinical use) had a similar effect. However, an action as CMA being the basis of inhibition of HR could not be confirmed in another 'allergy' model, namely HR from rat peritoneal mast cells (RPMC). PIC, TFP and two other CMA, W7 and N-(4-aminobutyl)-5-chloro-1-naphthalenesulfonamide) failed consistently to inhibit 48/80-induced HR from RPMC, and when used on their own at high concentration these compounds caused HR. PIC and TFP also potentiated the heat-induced haemolysis of rat erythrocytes, i.e. lacked membrane stabilizing effect in this model.
Agents and Actions 06/1991; 33(1-2):71-5.
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ABSTRACT: Deoxycholic acid (DA) caused a dose-related release of histamine (HR) from mast cells of rat peritoneum (RPMC) and mucosal cells of guinea pig rectocolon (RCMC). In both cell populations, DA-induced HR was: (1) accompared by a parallel release of lactate dehydrogenase (LDH), (2) not affected by metabolic inhibitors, (3) dependent on time of incubation, temperature and pH, and affected by Ca++ concentration in RPMC but not in RCMC. DA-induced HR from RCMC may be involved in certain functional disorders of the colon.
Agents and Actions 06/1991; 33(1-2):76-80.
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ABSTRACT: Urine concentrations of methylhistamine were measured in 11 subjects who experienced itching with chloroquine ('itchers') and in 14 who did not itch ('non-itchers'). In each group, urine methylhistamine concentrations were significantly greater at 12, 24 and 36 h after ingestion of 1 g chloroquine phosphate than before. There was no significant difference between itchers and non-itchers as regards urine methylhistamine concentrations at any time-point. Furthermore, there was no correlation between urine methylhistamine concentration and degree of pruritus in itchers. The findings suggest that histamine may be released by chloroquine, but it is unlikely to be the main cause of chloroquine-induced pruritus.
The Journal of tropical medicine and hygiene 01/1991; 93(6):423-5.
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ABSTRACT: The three currently available paper radioallergosorbent tests ('suxamethonium', alcuronium and thiopentone) were evaluated. 'Suxamethonium' radioallergosorbent test (which employs choline conjugated to paper discs) proved to be reliable in the detection of allergy to neuromuscular blockers, which were confirmed as the most common cause of anaphylactic reaction during general anaesthesia. Thiopentone radioallergosorbent test may also be useful, and is recommended in conjunction with 'suxamethonium' radioallergosorbent test in the preliminary investigation of reactions. Patients with positive 'suxamethonium' radioallergosorbent test usually require further testing, including alcuronium radioallergosorbent test, skin testing with a wide range of drug concentrations or leucocyte histamine release test.
Anaesthesia 01/1991; 45(12):1032-8. · 2.96 Impact Factor
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ABSTRACT: Renal vasoconstriction and ischaemia that follow in vitro antigen challenge of isolated perfused kidney of sensitized guinea-pig appears to be a self-perpetuating process, starting with a primary peak of release of vasoconstrictor mediators and followed by secondary peaks (particularly of arachidonic acid metabolites) which are probably initiated by ischaemia/reperfusion damage.
Agents and Actions 05/1990; 30(1-2):106-9.
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ABSTRACT: Histamine (Hi) release in vitro or in vivo in man was measured by variants of a radioimmunoassay (RIA) procedure. Hi released from isolated basophils was converted enzymically to N-tau-methylhistamine (NMH) which was then measured by a very sensitive RIA. This modified RIA was compared with the standard spectrofluorometric assay and was found to have additional advantages in certain applications. RIA of NMH in plasma was found to be of value in acute medical conditions of obscure aetiology.
Agents and Actions 05/1990; 30(1-2):287-90.
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ABSTRACT: Cyclosporin A (CS-A) partly inhibited IgE-mediated histamine release from human lung tissue in vitro (chopped and collagenase-dispersed preparations). Inhibition started at concentrations within the clinical blood level of the drug, but the IC50 was much higher (10-50 microM; 50% inhibition reached only in some experiments). CS-A also inhibited histamine release from rat peritoneal mast cells (RPMC) induced by antigen, concanavalin-A (Con-A), compound 48/80 and ionophore A23187. The IC50 values were 0.3, 23.0, and 33.0 microM for Con-A, A23187 and ovalbumin respectively. Inhibition of 48/80-induced release did not reach 50%. By comparison with human basophils the human lung and RPMC were less sensitive to the inhibitory action of CS-A. The IgE-mediated Schultz-Dale reaction in human lung strips was slightly and inconsistently inhibited by CS-A, but IgG1-mediated reaction in guinea-pig lung strips was potentiated by the drug.
Agents and Actions 05/1990; 30(1-2):110-3.
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ABSTRACT: IgG antibodies reacting with the quaternary ammonium group of choline and alcuronium appeared to be present in the sera of humans, guinea pigs, and rats. The antibodies, particularly those 'against' alcuronium, were detected in every serum by paper immunosorbent test(s). This finding, if substantiated, would be of fundamental importance in view of the wide distribution of choline derivatives within the body and in the environment. It may also be relevant to the histamine-releasing activity of neuromuscular blockers and compounds possessing the quaternary ammonium group.
International archives of allergy and applied immunology 02/1990; 91(4):426-30.
