E. Giannella

Histamine release from rat mast cells induced by metabolic activation of polyunsaturated fatty acids into free radicals

Polyunsaturated fatty acids (PUFA: arachidonic and linoleic acid) release histamine from isolated purified rat serosal mast cells only in the presence of oxidizing systems such as phenobarbital-induced rat liver microsomes, prostaglandin-H-synthetase (PHS) or soybean lipoxygenase. The release of mast cell histamine by activated PUFA has a long time-course and the electron microscopical features are consistent with an exocytotic secretion in the case of arachidonic acid and cell lysis in the case of linoleic acid. The phenomenon is associated with a significant increase in malonyldialdehyde (MDA) and conjugated diene generation, suggesting a relationship between histamine release and membrane lipid peroxidation. The secretion of histamine was inhibited by anti-free radical interventions such as D-mannitol, reduced glutathione and alpha-tocopherol. Some cyclooxygenase and lipoxygenase inhibitors, cimetidine and carnitine derivatives, are differentially active in the inhibition of mast cell histamine release by activated arachidonic acid. These results suggest that free radical derivatives of PUFA, generated by metabolic activation, trigger mast cell histamine release.

Histamine and lactate dehydrogenase (LDH) release in ischemic myocardium of the guinea-pig.

Histamine has been proved to be released during myocardial infarction and ischemic arrhythmias in dogs. The aim of the present experiments was to evaluate if ischemia and reperfusion modify histamine and lactate dehydrogenase (LDH) release in isolated guinea-pig heart. The results obtained show a steady increase of LDH release both in the ischemic and reperfusion phases. The release of histamine was reduced during the ischemic phase and increased significantly during reperfusion. A significant diminution of mast cell granule metachromasia was observed in the right auricles at the end of the reperfusion period. D-mannitol and reduced glutathione (GSH) modified the kinetics of histamine and LDH release. Cimetidine was able to decrease significantly the release of histamine during the ischemic and reperfusion phases and also reduced the release of LDH; triprolidine was completely ineffective. The results suggest that oxygen-derived free radicals may be involved in the pathogenesis of myocardial dysfunction after ischemia and reperfusion.

Stimulation and resection of Vidian nerve in patients with chronic hypertrophic non-allergic rhinitis: effect on histamine content in nasal mucosa

Parasympathetic innervation of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.). The present study investigated the effect of Vidian nerve stimulation and resection on the histamine contents and on the morphological pattern in mucosal samples of patients with C.H.N.A.R. Vidian nerve stimulation determines a significant decrease in histamine content in the samples examined; microscopical observations showed significant variations in the glandular, stromal and vascular components.The changes indicate an enhanced secretory activity, intensive vasodilatation and active degranulation of mast cells, which were significantly decreased in number in the samples obtained after 90 sec of stimulation.The neurectomy of the Vidian nerve resolves quite completely the clinical symptomatology and in parallel decreases the mucosal histamine contents, which are increased in patients with C.H.N.A.R. before the operation in comparison with the normal controls.

Vidian nerve resection, histamine turnover and mucosal mast cell function in patients with chronic hypertrophic non-allergic rhinitis

Parasympathetic innervation of the respiratory tract of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.), the vidian nerve providing the main parasympathetic nerve supply to respiratory mucosa. The present study investigates the effect of vidian nerve resection in 22 patient with intractable C.H.N.A.R. on histamine content and formation and on the number of mast cells and their degranulation in the respiratory tract. Samples were taken from respiratory mucosa for histamine and histidine-decarboxylase assay, and for microscopic observations for mast cell density and degranulation index, before and 12–24 months after vidian nerve resection. Neurectomy of the vidian nerve completely cured the clinical symptomatology, evaluated by rhinoreomanometry, and also significantly decreased both the high histamine levels and histidine-decarboxylase activity in patients with C.H.N.A.R. The density and degranulation index of mast cells were also significantly lower after surgery. These data suggest a relationship between cholinergic activity and the secretory response of mast cells and indicates a correlation between the parasympathetic nerve supply and chronic hyperthrophic non-allergic rhinitis. The significant reduction in mast cell density, histamine levels and histidine-decarboxylase activity also lends support to the hypothesis that the parasympathetic nerve supply plays a role in the regulation of mast cell histamine.

Ischemia-reperfusion injury and histamine release in isolated guinea-pig heart: the role of free radicals.

Free radicals produced by the occlusion and opening of the left anterior descending coronary artery and/or by perfusion of isolated guinea-pig heart with FeCl3/ADP (10 μM/100 μM) induce a differential release of histamine and lactate dehydrogenase (LDH) in the perfusates with a preferential liberation of histamine in the reperfusion phase, associated with an increase of ventricular arrhythmias. The release of histamine has been correlated with malonyldialdehyde (MDA) production and tissue calcium content in left ventricular tissue. MDA increased during ischemia, while the calcium content increased when the tissue was reperfused. Under these conditions, N-t-butyl-α-phenylnitrone (BPN), a molecule capable of forming spin adducts with free radicals, andd-mannitol are active in preventing reperfusion-induced arrhythmias.

Histamine release by platelet aggregation.

Coincubation of rat serosal mast cells with human platelets leads to a significant release of histamine, which dose-dependently increases when platelet aggregation is induced by various concentrations of arachidonic acid. In turn, histamine enhances platelet aggregation induced by different agonists, this effect being mimicked by pyridyl-ethyl-amine (PEA), blocked by mepyramine and amplified by ranitidine. The data suggest the existence of a platelet-derived histamine releasing factor (PDHRF) and indicate the presence of platelet H1 and H2 receptors, capable of modulating platelet aggregation.

Mast Cell Histamine Release Induced by Intermediate Products of Arachidonic Acid Metabolism

This study was performed to evaluate the role of intermediate products of arachidonic acid metabolism on histamine release from rat serosal mast cells. Arachidonic acid in concentrations ranging from 10(-9) to 10(-4) M caused no histamine release from purified rat peritoneal mast cells. High concentrations (10(-6)-10(-6) M) of the terminal products of the arachidonic acid metabolism were also devoid of any significant histamine-releasing properties. The metabolic activation of arachidonic acid with prostaglandin-H-(PGH)-synthase isolated from calf seminal vesicles, evoked a significant release of histamine from rat serosal mast cells. The liberation of histamine was not accompanied by a significant leakage of lactic dehydrogenase (LDH) and the electron microscopical features were consistent with an exocytotic release. The phenomenon was blocked by reduced glutathione (GSSH) and by D-mannitol, a hydroxyl free-radical scavenger. These results suggest that free radical derivatives of arachidonic acid are generated during the catalysis which triggers mast cell histamine release.

Histamine release from nasal mucosal mast cells in patients with chronic hypertrophic non-allergic rhinitis, after parasympathetic nerve stimulation

The vidian nerve provides the main parasympathetic nerve supply to nasal respiratory and maxillary sinus mucosa, and its electrical stimulation causes apparent secretory and vasodilatatory effects in animals.The present investigation was carried out in 8 patients with chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.) undergoing therapeutic vidian nerve resection. The vidian nerve was electrically stimulated before the resection. Samples were taken from nasal sinus mucosa for histamine determination and microscopical observation before and after the stimulation period. Vidian nerve stimulation causes a significant decrease in histamine content and mast cell density in the mucosa sample, differentially influenced by eserine and atropine pretreatment.

The antianaphylactic action of histamine H2‐receptor agonists in the guinea‐pig isolated heart

1 The effects of histamine and of H1‐and H2‐receptor agonists on the response to specific antigen were studied in isolated hearts taken from actively sensitized guinea‐pigs. 2 Histamine and H2‐receptor agonists (dimaprit, impromidine) dose‐dependently decrease the positive chronotropic and inotropic effects, and the severity of arrhythmias evoked by the challenge of sensitized hearts with specific antigen. 3 Nordimaprit and the selective H1‐receptor agonist 2‐pyridyl‐ethyl‐amine (2‐PEA) did not modify the patterns of cardiac anaphylaxis. 4 The positive inotropic and chronotropic responses of the isolated heart to exogenous histamine appear to be partly reduced in the presence of dimaprit. 5 The H2‐receptor agonists decrease the amount of histamine released during cardiac anaphylaxis which is increased by cimetidine, while nordimaprit and PEA were ineffective, indicating an inhibitory function afforded by H2‐receptors in cardiac anaphylaxis.

Histamine release in acute coronary occlusion-reperfusion in isolated guinea-pig heart.

It has been shown that plasma histamine significantly increases during myocardial infarction in the dog. Histamine is also released when the isolated guinea-pig heart is reperfused after 30 minutes of low flow perfusion. The release of histamine and lactate dehydrogenase (LDH) after left anterior descending coronary artery ligation and release were investigated in the present study and related to the changes in electrocardiographic parameters and to a computer-aided analysis of left ventricular mast cell metachromasia.Spontaneous release of histamine was unchanged during ischemia and increased after the release of the ligature, while we observed a steady increase of LDH overflow. In parallel, a significant diminution of mast cell granule metachromasia was observed in left ventricular samples.The perfusion of the heart with FeCl3/ADP (10 μM/100μM), a free radical-generating system, significantly enhanced both the basal and ischemic-reperfusion release of histamine, while perfusion with N-t-butyl-phenyl-nitrone (BPN/100 μM) a “spin-trapper” molecule, significantly decreased histamine and LDH release and the loss in metachromasia of left ventricular mast cells induced by reperfusion. Inhibitors of xanthine oxidase (allopurinol, 10 μM) and of calcium-activated proteases (leupeptin, 10 μM) modified the kinetics of histamine and LDH release.