Pathophysiological insights into delayed pressure urticaria: A comprehensive review.

The in vitro histamine release response of human intestinal mast cells and basophils challenged with anti-IgE, Concanavalin A, ionophore A23187 and food extracts was compared with skin prick test, RAST analysis and open food challenge. It was not possible to perform food challenge in all patients; however, seven children underwent open food challenge and in five the clinical diagnosis of "true" food allergy was confirmed. The intestinal mast cells were pooled from enzymatically dispersed duodenal biopsies obtained by duodenoscopy from 15 selected children suspected of food allergy, and five age-matched controls. In nine of 10 patients classified as "food allergic" intestinal mast cells released histamine to various food extracts in a dose-dependent fashion. From the mast cells of the nine food-allergic patients compared with non-allergics, the anti-IgE mediated mast cell histamine release was increased. Additionally, at 1000 U/ml anti-IgE the mast cell histamine release was increased compared with their corresponding basophils. However, in non-allergic subjects the histamine release of basophils was increased compared with their corresponding mast cells. Histamine release from basophils was positively correlated to the test scores of the RAST analysis, skin prick test, and food challenge. No apparent correlation between tests scores obtained from histamine release of intestinal mast cell and the other tests was demonstrated, except in children with diarrhoea as only symptom. However, the study gives evidence that duodenal mast cells actually are sensitized with specific IgE and thus may play a pathophysiological role in food hypersensitivity. In addition, the study shows that the ability of different stimuli, including food extracts, to trigger basophil histamine release does not correlate with their potency to induce histamine release from mast cells.

Carnosine (beta-alanyl-histidine) is a naturally occurring dipeptide that has been characterized as a putative hydrophilic antioxidant. The protective function of carnosine has been demonstrated in neuronal cells under ischemic injury. The purpose of this study was to investigate the effects of carnosine on oxygen-glucose deprivation (OGD)-induced degranulation and histamine release from mast cells. Cultured mast cells were exposed to OGD for 4 h, and then the degranulation was observed immediately by microscopy. Histamine release was analyzed by high-performance liquid chromatography (HPLC). OGD caused degranulation of mast cells, and increased histamine and lactate dehydrogenase (LDH) release. Carnosine (at a concentration of 5 mM) alone did not produce any appreciable effect on degranulation, histamine, and LDH release from mast cells under normal condition, but significantly inhibited the degranulation, histamine, and LDH release of mast cells induced by OGD. These results indicate that carnosine can protect mast cells from degranulation and histamine release and it may be an endogenous mast cell stabilizer in the pathological processes induced by ischemia.

Mast cells participate in allergies and inflammation by secreting a variety of pro-inflammatory mediators. Curcumin, the active component of turmeric, is a polyphenolic phytochemical with anti-tumor, anti-inflammatory, anti-oxidative, and anti-allergic properties. The effects of curcumin on compound 48/80-induced mast cell activation and passive cutaneous anaphylactoid reactions are unknown. In this report, we investigated the influences of curcumin on the passive cutaneous anaphylactoid response in vivo and compound 48/80-induced mast cell activation in vitro. The mechanism of action was examined by calcium uptake measurements and cAMP assays in mast cells. Curcumin significantly attenuated the mast cell-mediated passive cutaneous anaphylactoid reaction in an animal model. In agreement with this in vivo activity, curcumin suppressed compound 48/80-induced rat peritoneal mast cell (RPMC) degranulation and histamine release from RPMCs. Moreover, compound 48/80-elicited calcium uptake into RPMCs was reduced in a dose-dependent manner by curcumin. Furthermore, curcumin increased the level of intracellular cAMP and significantly inhibited the compound 48/80-induced reduction of cAMP in RPMCs. These results corroborate the finding that curcumin may have anti-allergic activity.

IT HAS BEEN SHOWN THAT, DEPENDING UPON THEIR CONCENTRATION, ANTIHISTAMINES ACT IN THREE DIFFERENT WAYS: (a) by competitive inhibition of histamine as already known; (b) by destroying mast cells and releasing histamine; and (c) by preventing mast cell damage and histamine release in anaphylaxis. Furthermore, antihistamines potentiated mast cell damage and histamine release by compound 48/80, when acting on guinea-pig tissues, and inhibited these same phenomena when acting on rat tissues. It is concluded that the effect of antihistamines in anaphylaxis is possibly due both to their competitive inhibition of histamine on smooth muscle receptors and to their inhibition of mast cell damage and histamine release by antigen.

Release of histamine and tryptase during continuous and interrupted cutaneous challenge with allergen in humans

Mast cell activation by pedicellarial toxin of sea urchin, Toxopneustes pileolus

Mast cell histamine release is considered to be associated with the etiology of anaphylactoid reactions to iodinated radiographic contrast media (RCM). In the present study, the effects of various ionic and non-ionic RCM on histamine release from mast cells were compared, and the possible mechanisms of the histamine release were subsequently determined. Both ionic (ioxaglate and amidotrizoate) and non-ionic (iohexol, ioversol, iomeprol, iopamidol and iotrolan) RCM increased histamine release from the dissociated rat pulmonary cells, whereby ionic materials were more potent than non-ionic agents. There was no significant correlation between the extent of histamine release and the osmolarity of each RCM solution. In addition, hyperosmotic mannitol solution (1000 mOsm/kg) caused no marked histamine release. Thus, it is unlikely that the hyperosmolarity of RCM solutions contributes to the histamine release. RCM also stimulated, but to a lesser extent, the histamine release from rat peritoneal cells. The RCM-induced histamine release from both types of cells was inhibited by dibutyl cyclic AMP or combined treatment with forskolin and 3-isobutyl-1-methylxanthine. Corresponding to these results, RCM markedly reduced the cellular cyclic AMP content. On the other hand, the removal of intracellular but not the extracellular Ca2+ attenuated the RCM-induced mast cell histamine release. From these findings, it is suggested that the decrease in cellular cyclic AMP content and an increase in intracellular Ca2+ contribute at least in part to the RCM-induced mast cell histamine release.

A rationale for the use of nedocromil sodium in the treatment of asthma

Kounis syndrome (KS) is an acute coronary syndrome triggered by allergic or hypersensitivity reactions. Incidence rates vary, with studies reporting 19.4 per 100.000 among all admissions and 3.4% among allergy patients. This review explores the expanding understanding of KS, encompassing various manifestations, and focusing on both clinical data and forensic findings useful in performing a diagnosis. The pathophysiology of this syndrome involves a complex interplay between allergic reactions and the cardiovascular system. Mast cell activation, histamine release, leukotrienes, cytokines, and platelet activation can contribute to coronary events. Three types of classification systems (allergic angina, allergic myocardial infarction, allergic stent thrombosis) aid in categorizing presentations. The diagnosis of KS relies on clinical presentation, laboratory findings, and imaging. Postmortem assessment of KS is based on the integration of circumstantial data, autopsy, and histological findings. Biochemical and immunohistochemical analyses also contribute to postmortem diagnosis. In conclusion, a combined, multidisciplinary approach should be used to ease the diagnostic process, which is crucial for forensic practitioners in confirming KS occurrence.

The effect of aging on mast cell secretory function was studied in young (8 weeks old) and aged (72 weeks old) female BD6 rats using passive cutaneous anaphylaxis (PCA) and the histamine release testin vitro. Young rats were more susceptible to PCA and their peritoneal mast cells released more histamine in anin vitro anaphylactic reaction. Measurement of electron spin resonance (ESR) using methyl-5-doxylstearate and methyl-16-doxylstearate as spin labels demonstrated that cell membranes of mast cells of young rats showed higher fluidity in the resting state and a more pronounced increase in membrane fluidity after anaphylactic stimulation than mast cell membranes of aged rats. The study of lipid composition of mast cell membranes showed that the ratio of cholesterol (C) to phospholipids (P) was lower in mast cells of young rats than in mast cells of aged rats. This suggests that a decrease in membrane fluidity, associated with an increase in C/P ratio may be one of the factors responsible for decreased histamine releasability of mast cells from aged rats.

Activation and inhibition of mast cells degranulation affect their morphometric parameters

Antigen inhalation induces mast cells and eosinophils infiltration in the guinea pig esophageal epithelium involving histamine-mediated pathway

The metabolic activation of morphine, cocaine and methadone into free radicals could have pathophysiological relevance in the organic injuries of drug addiction.Isolated purified rat serosal mast cells were incubated with morphine, cocaine and methadone (10(-7) M-10(-4) M) with oxidative enzymes (prostaglandin-H-synthetase, 25 mU; rat liver homogenate fraction S 10-mix, 400 microl), and with the drugs of abuse in the presence of oxidative enzymes. Histamine and lactate dehydrogenase (LDH) were analysed with a fluorimetric and spectrophotometric assay, respectively; the generation of malonyldialdehyde (MDA) was measured by a spectrophotometric assay.The release of mast cell histamine and the generation of MDA are present only when mast cells were incubated with the drugs of abuse in the presence of oxidative enzymes. This release was dependent on the concentration of the drug in question and showed a maximum value at 10(-4) M. Moreover, in parallel experiments we demonstrated that, under the same experimental conditions, the release of LDH was always less than 20% of the total, suggesting that this effect is due to a selective exocytotic process. Histamine release and MDA generation were abated by the free radical scavengers: reduced glutathione, 10(-4) M GSH and alpha-tocopherol, 10(-4) M and by the spin trapper 5.5-dimethyl-1-pyrroline-N-oxide, 10(-4) M DMPO. The light and electron microscopic features are consistent with exocytotic secretion in the cases of morphine and methadone and with cell lysis in the case of cocaine.These results suggest that morphine, cocaine and methadone are activated into free radicals which produce membrane lipid perturbation and histamine release, suggesting that a massive release of mast cell histamine could be an additional risk factor in heroin and cocaine overdoses.

The metabolic activation of morphine, cocaine and methadone into free radicals could have pathophysiological relevance in the organic injuries of drug addiction. Isolated purified rat serosal mast cells were incubated with morphine, cocaine and methadone (10(-7) M-10(-4) M) with oxidative enzymes (prostaglandin-H-synthetase, 25 mU; rat liver homogenate fraction S 10-mix, 400 microl), and with the drugs of abuse in the presence of oxidative enzymes. Histamine and lactate dehydrogenase (LDH) were analysed with a fluorimetric and spectrophotometric assay, respectively; the generation of malonyldialdehyde (MDA) was measured by a spectrophotometric assay. The release of mast cell histamine and the generation of MDA are present only when mast cells were incubated with the drugs of abuse in the presence of oxidative enzymes. This release was dependent on the concentration of the drug in question and showed a maximum value at 10(-4) M. Moreover, in parallel experiments we demonstrated that, under the same experimental conditions, the release of LDH was always less than 20% of the total, suggesting that this effect is due to a selective exocytotic process. Histamine release and MDA generation were abated by the free radical scavengers: reduced glutathione, 10(-4) M GSH and alpha-tocopherol, 10(-4) M and by the spin trapper 5.5-dimethyl-1-pyrroline-N-oxide, 10(-4) M DMPO. The light and electron microscopic features are consistent with exocytotic secretion in the cases of morphine and methadone and with cell lysis in the case of cocaine. These results suggest that morphine, cocaine and methadone are activated into free radicals which produce membrane lipid perturbation and histamine release, suggesting that a massive release of mast cell histamine could be an additional risk factor in heroin and cocaine overdoses.

1. Isolated purified rat serosal mast cells were incubated with given concentrations of drugs of abuse (morphine, cocaine, methadone), with oxidative enzymes (prostaglandin-H-synthetase, PHS; rat liver homogenate fraction - S-10 mix), and with the drugs of abuse in the presence of oxidative enzymes. 2. The release of mast cell histamine and the generation of malonyl-dialdehyde (MDA) is present only when mast cells were incubated with the drugs of abuse in the presence of oxidative enzymes. 3. The release of histamine and the generation of MDA were abated by the free radical scavengers, reduced glutathione (GSH) and α-tocopherol. 4. It is suggested that morphine, cocaine and methadone are activated into free radicals producing membrane lipid perturbation and histamine release. 5. The metabolic activation of morphine, cocaine and methadone into free radicals could entail pathophysiological relevance in the organic injuries of drug addiction.