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Histamine incorporation into murine myeloblasts and promyelocytes. Formation of a histamine transport system.

When isolated murine myeloblasts and promyelocytes were treated with 3H-histamine (5 x 10(-7) M) in RPMI-1640 medium supplemented with 20% horse serum at 37 degrees, the radioactivity of these cells increased gradually, reaching a maximum after 6 hr. However, when these progenitor cells were pretreated with unlabeled histamine (5 x 10(-7) M) for 1 hr, subsequent exposure to 3H-histamine caused prompt incorporation, the extent of which was more than 3.8 times that seen in cells which were not pretreated. This acceleration was prevented by simultaneous addition of cycloheximide (4 x 10(-7) M) or actinomycin D (10(-7) M) in the pre-incubation stage. While the microsomal fraction of progenitor cells pretreated with histamine initially yielded a higher binding capacity, that of the plasma membrane fraction rose significantly after 1 hr. Most of the incorporated 3H-histamine was detected as unmetabolized. Non-histone chromatin protein had a higher affinity to 3H-histamine than did the DNA fraction of progenitor cell nuclei. Histamine inhibited myeloperoxidase activity of myeloid progenitor cells selectively and dose-dependently without affecting eosinophil peroxidase. These findings suggest that histamine incorporated into murine myeloblasts and promyelocytes induces the synthesis of a specific protein(s) through interaction with the nucleus, and that these proteins, in turn, may be combined into the cell membrane, where they act as a transport system for histamine incorporation.

Animals↗

Effect of histamine and histamine antagonists on natural and antibody-dependent cellular cytotoxicity of human lymphocytes in vitro.

The in vitro effect of histamine and its antagonists, cimetidine and clemastine fumarate, on natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities of human lymphocytes was investigated. The histamine 1 (H1) antagonist, clemastine fumarate, and the histamine 2 (H2) antagonist, cimetidine, but not histamine alone, inhibited the NK and ADCC activities of lymphocytes when added directly to the mixture of effector and target cells in a 51Cr-release assay. This inhibition was proportional to the concentration of drugs added and was observed at various effector to target ratios against several targets. H1 and H2 antagonists also inhibited NK activities of T cells as well as Percoll-separated, NK-enriched effector cells. The inhibition was significantly reversed by histamine. In target binding assays, clemastine fumarate and cimetidine also decreased the target binding capacity of effector lymphocytes. Further, PBL precultured with histamine (10(-3)-10(-4) M) for 24 hr showed a significant decrease in their NK and ADCC activities. In coculture experiments, PBL precultured with histamine suppressed the NK activity of normal autologous effector lymphocytes. PBL precultured with histamine showed an increased number of OKT8+ cells, as estimated using monoclonal antibodies. The suppression of cytotoxicity was not due to either direct toxicity, steric hindrance, crowding, or cell death, but by functionally viable suppressor cells. An immunoregulatory role for histamine in NK and ADCC reactions is proposed.

Adult↗

Simple and rapid determination of histamine in food using a new histamine dehydrogenase from Rhizobium sp.

A colorimetric enzyme assay for the quantitative analysis of histamine in food has been developed using a new histamine dehydrogenase (HDH) from Rhizobium sp. The HDH specifically catalyzes the oxidation of histamine but not other biogenic amines such as putrescine and cadaverine. The principle of our photometric assay is as follows. The HDH catalyzes the oxidative deamination of histamine in the presence of 1-methoxy PMS (electron carrier), which converts WST-8 (tetrazolium salt) to a formazan. This product is measured in the visible range at 460 nm. The correlation between the histamine level and absorbance was acceptable, ranging from 0 to 96 microM with histamine standard solutions, corresponding to 0 to 30 microM of the reaction solution (r = 1.000, CV = 1.0% or less). Assays of canned tuna (in oil and soup) and raw tuna with 45-675 micromol/kg histamine added showed good recoveries of 96-113, 98-108, and 100-106%. The histamine contents of a commercial canned tuna and fish meal containing histamine at high concentrations were determined using the new method and other reference methods (HPLC method, Association of Official Analytical Chemists official method, and two commercial enzyme immunoassay test kits). This simple and rapid enzymatic method is as reliable as the conventional methods.

Animals↗

Passive sensitization and histamine release of basophils. IgE and cellular factors regulating histamine release.

This study had two purposes. First, to examine a possible functional heterogeneity of IgE regulating basophil histamine release and the effect of using two different donor cells for passive sensitization experiments. Second, to investigate basophils not releasing histamine to anti-IgE by stimulating protein kinase C with the addition of the phorbol-ester, TPA. In consecutive experiments responding donor basophils were passively sensitized with plasma from non-responding subjects. Thus, the first set of experiments included passive sensitization of acid treated donor basophils from one atopic and one non-atopic patient with plasma from 29 children with exogenous asthma to grass pollen, cat dander, or dust mites. Different secretagogues (anti-IgE, Concanavalin A, and N-formyl-methionyl-leucyl-phenylalanine) induced different histamine release responses due to a cellular property of the basophils not related to the type of IgE bound to the cell membrane. It was demonstrated that the allergen-induced histamine release did not depend on the extract or type of IgE when the biological activity of each extract and serum-specific IgE levels were similar. However, the atopic donor cells released significantly (P less than 0.05) more histamine than non-atopic donor cells. Thus, histamine release depends on the type of secretagogues and a cellular property which is maybe influenced by the presence of serum factors and a certain type of IgE in the serum of atopics. The second set of experiments included 10 patients (6 atopics and 4 non-atopics) with non-histamine releasing basophils. In the presence of 10 ng/ml TPA, however, seven of 10 patients released histamine at anti-IgE challenge. Three months later two additional patients became responsive in the presence of TPA. By passive sensitization of responding donor basophils the non-responding patients were shown to possess functionally intact IgE. Thus, the discrepancies sometimes observed between clinical symptoms, serological IgE-antibody measurements and histamine release testing in allergic patients may be related to a cellular property of basophils.

Adolescent↗

Endotoxin-induced hypersensitivity to histamine in mice. I. Contrasting effects of bacterial lipopolysaccharides and the classical histamine-sensitizing factor of Bordetella pertussis.

Pieroni, Robert E. (Massachusetts Department of Public Health, Boston), Edward J. Broderick, and Leo Levine. Endotoxin-induced hypersensitivity to histamine in mice. I. Contrasting effects of bacterial lipopolysaccharides and the classical histamine-sensitizing factor of Bordetella pertussis. J. Bacteriol. 91:2169-2174. 1966.-The capacity of typhoid and possibly of pertussis endotoxins to induce histamine-shock susceptibility in some of the mice that survive graded doses of these endotoxins was confirmed. It was demonstrated, however, that pertussis endotoxin cannot be the main source of the typical histamine sensitization of pertussis vaccine. The following points are made. (i) With typhoid and pertussis endotoxins as inducers of histamine shock, no systematic relation between deaths and induction dose could be found, and 100% mortality could not be achieved. In contrast, with pertussis protective fraction as inducer, there was clear dose-response regression, with 100% mortality possible. (ii) The major part of the histamine-sensitizing activity of pertussis vaccine or its extracts was destroyed by trypsinization or by heating for 30 min at 100 C. These processes do not affect the histamine-sensitizing activity of the endotoxins. The implication for purified pertussis vaccine with high histamine-sensitization capacity is that endotoxin need not necessarily be present. The significance and possible mechanisms of action of endotoxin-induced histamine sensitivity are briefly discussed.

Animals↗

Interleukin-8 and RANTES inhibit basophil histamine release induced with monocyte chemotactic and activating factor/monocyte chemoattractant peptide-1 and histamine releasing factor.

The objective of this study was to investigate the effect of interleukin-8 (IL-8) and RANTES on basophil histamine release induced with monocyte chemoattractant peptide-1 (MCP-1) and crude histamine releasing factor (HRF). IL-8 induced low levels of histamine release (8.5 +/- 0.5%) from basophils obtained from only six of 20 donors at high concentrations (10(-6) M). RANTES induced histamine release (16 +/- 2%) from basophils of four of 15 donors at 10(-7) M concentration. However, both IL-8 and RANTES inhibited MCP-1 and HRF-induced histamine release from basophils dose-dependently at concentrations of 10(-9) to 10(-7) M. Basophils from all donors showed a significant inhibitory response (greater than 15%). The maximal inhibition of MCP-1 and HRF by IL-8 was 28 +/- 4% and 48 +/- 8%, respectively. The maximal inhibition of MCP-1 and HRF by RANTES was 26 +/- 4% and 43 +/- 6%, respectively. Peripheral blood mononuclear cell-derived HRF was purified into three distinct peaks by reverse-phase high performance liquid chromatography. Peak I contained MCP-1 as judged by binding to an immunoaffinity column that was prepared with anti-MCP-1 antibody. IL-8 inhibited histamine release induced with all three peaks of HRF. The inhibition of histamine release by IL-8 was significantly higher in normal subjects than in allergic patients (59 +/- 9% versus 31 +/- 7%, P less than 0.05). Both IL-8 and RANTES inhibited cytokine-induced histamine release only and did not affect histamine release by anti-IgE, FMLP, and C5a.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Infective Agents↗

Histamine and the stomach: chemical histamine assays.

Histamine assays in gastroduodenal tissues and body fluids are not an absolute objective of scientific interest but are related to the role of histamine in health and disease. Hence, the reliability of histamine assays has to be assessed in relation to this aim. Sensitivity and specificity of the chemical histamine assays are similar in tissues and body fluids. The modern developments in a fluorometric-fluoroenzymatic assay guarantee the highest sensitivity and specificity, especially by tests that monitor specificity in each single run of histamine determinations. Precision and accuracy of histamine measurement were especially investigated for the fluorometric assay. They included tests on the coefficient of variation over the whole concentration range, long-term precision with double-sample standard control charts, comparison of several methods for histamine assay including bioassay, and long-term accuracy with the use of Cusum charts. Finally, appropriate sample preparation, sample-taking, relevant body fluids and tissues, and the right time for sample-taking were evaluated in extended methodologic studies. Histamine assays are not just methods for a normal routine laboratory. Extended knowledge about histamine release and metabolism will be necessary to analyse data in this particular field with reasonable validity.

Animals↗

Formation of histamine and biogenic amines in cold-smoked tuna: an investigation of psychrotolerant bacteria from samples implicated in cases of histamine fish poisoning.

Two outbreaks and a single case of histamine fish poisoning associated with cold-smoked tuna (CST) were reported in Denmark during 2004. The bacteria most likely responsible for histamine formation in CST implicated in histamine fish poisoning was identified for the first time in this study. Product characteristics and profiles of biogenic amines in the implicated products were also recorded. In the single poisoning case, psychrotolerant Morganella morganii-like bacteria most likely was responsible for the histamine production in CST with 2.2% +/- 0.6% NaCl in the water phase (WPS). In outbreak 1, Photobacterium phosphoreum most likely formed the histamine in CST with 1.3% +/- 0.1% WPS. In outbreak 2, which involved 10 persons, the bacteria responsible for histamine formation could not be determined. The measured concentrations of WPS were very low compared with those of randomly collected commercial samples of CST and cold-smoked blue marlin (4.1 to 12.7% WPS). Challenge tests at 5 degrees C with psychrotolerant M. morganii and P. phosphoreum in CST with 4.4% WPS revealed growth and toxic histamine formation by the psychrotolerant M. morganii-like bacteria but not by P. phosphoreum. In a storage trial with naturally contaminated CST containing 6.9% WPS, lactic acid bacteria dominated the microbiota, and no significant histamine formation was observed during the shelf life of about 40 days at 5 degrees C and of about 16 days at 10 degrees C. To prevent toxic histamine formation, CST should be produced with >5% WPS and distributed with a declared 5 degrees C shelf life of 3 to 4 weeks or less.

Animals↗

Histamine leukocytosis. I. Effect of histamine on peripheral leukocyte counts.

The effect of chronic administration of histamine on the number of cells in peripheral blood of dogs, rabbits and guinea pigs was tested by single and consecutive intramuscular injections of histamine in a beeswax-sesame oil mixture. Leukocytosis due to increased numbers of neutrophils occurred in all animals after single injections of histamine in beeswax, although erythrocytes and hematocrit values were unaffected in all species. When injection of histamine was repeated on consecutive days, the extent of leukocytosis subsided in some cases; however, the simultaneous administration of aminoguanidine restored leukocytosis. Single or daily injections of the beeswax-sesame oil mixture without histamine had none of these effects in any animals tested. Although simultaneous injections of histamine and H1 receptor antagonists did not alter histamine effects, the combined administrations of histamine and H2 receptor blocking agents suppressed histamine-induced leukocytosis.

Animals↗

Lysine200 located in the fifth transmembrane domain of the histamine H1 receptor interacts with histamine but not with all H1 agonists.

Previously, we have shown that asparagine207 in the fifth transmembrane domain of the histamine H1 receptor is crucial for the binding of the N tau-nitrogen of the imidazole ring of histamine (Leurs et al., Biochem. Biophys. Res. Commun., 201, 295, 1994). In view of the potential interaction of the imidazole ring of histamine with a binding site, formed by asparagine207 and lysine200, we mutated lysine200 in the fifth transmembrane domain of the histamine H1 receptor to a non-functional alanine residue. This mutation did not affect the binding of the tested H1 receptor antagonists but resulted in a 5-fold lower affinity for histamine. The binding of other H1 receptor agonists was not affected. In stably transfected CHO cells histamine was 55-fold less effective in activating the H1Lys200Ala receptor (EC50 = 66 microM) compared to the wild type H1 receptor (EC50 = 1.2 microM). Receptor activation by the 2-methyl and the 2-(3-bromophenyl)-analogues however was hardly affected by the mutation, indicating that the 2-substituent probably prevents the interaction with the lysine200 residue. Finally, the Lys200Ala mutation reduced the production of [3H]inositol phosphates, stimulated by the non-imidazole H1 receptor agonist 2-pyridylethylamine. These data indicate that lysine200 interacts with the N pi-nitrogen of histamine and is important for the activation of the H1 receptor by histamine and the non-imidazole agonist 2-pyridylethylamine.

Amino Acid Sequence↗

A modulation of the anaphylactic basophil histamine release by selective H2 histamine agonists.

Two selective H2-histamine agonists, dimaprit and impromidine, have been tested for their action on histamine release from human basophils and rat mast cells. IgE-mediated basophil histamine release was inhibited by stimulation of histamine H2-receptors. However, differences between the actions of both dimaprit and impromidine were noticed. Both impromidine and dimaprit had no specific effect on 48/80-induced histamine release from rat mast cells, although the latter in higher concentrations either slightly increased spontaneous histamine release or non-specifically inhibited compound 48/80-induced release. The results are consistent with the view that activation of adenylate cyclase via H2-histamine receptors might be an important regulatory mechanism of histamine release from human basophils but not from rat mast cells.

Allergens↗

Differential effects of histamine mediated by histamine H1- and H2-receptors on contractility, spontaneous rate and cyclic nucleotides in the rabbit heart.

The effects of histamine on the contractile force, spontaneous rate of contraction, and cyclic AMP and cyclic GMP content were investigated in isolated rabbit cardiac preparations. Histamine had a positive inotropic effect in the left atrium and papillary muscle, and a positive chronotropic effect in the right atrium. Both effects were produced in a concentration-dependent manner. Impromidine also induced the same effect in the left and right atrium as histamine did. The effects produced by histamine and impromidine were antagonized by cimetidine and tiotidine. On the other hand, the positive inotropic response of papillary muscle to histamine was antagonized by mepyramine and chlorpheniramine and was mimicked by 2-(2-pyridyl)ethylamine. Impromidine at a high concentration induced a small increase in the contractile force, an effect which was antagonized by cimetidine. Histamine significantly increased the cyclic AMP levels in both atria but not in papillary muscles. The increase in cyclic AMP was abolished by cimetidine. Histamine also increased cyclic GMP levels in all of the preparations. The increase in cyclic GMP was abolished by chlorpheniramine. The results suggest that both H1- and H2-receptors exist in all parts of the rabbit heart. However, the positive inotropic and chronotropic effects induced by histamine in left and right atrium are mediated predominantly via H2-receptors, whereas the positive inotropic effect in papillary muscle is predominantly mediated via H1 receptors.

Animals↗

In vitro effect of histamine and histamine H1 and H2 receptor antagonists on cellular proliferation of human malignant melanoma cell lines.

Histamine is an established growth factor for gastric and colorectal cancer. Contradictory data for response of melanoma to histamine have been reported. Our aims were to determine the effect of histamine and H1 and H2 receptor antagonists on cell growth and cyclic AMP production. Four human melanoma cell lines were cultured with a range of concentrations of histamine, and with the H2 receptor antagonists cimetidine, ranitidine or famotidine, or the H1 receptor antagonist diphenhydramine. Cellular proliferation was measured by the uptake of [3H]-thymidine. Cyclic AMP production was also measured to determine the receptor status of the cell lines. Histamine significantly stimulated growth in two of four cell lines, with maximal stimulation at 1 x 10(-8) M. This effect was inhibited by all four antagonists in a dose-dependent manner. Histamine [10(-7) to 10(-4) M] also induced a dose-dependent increase in cyclic AMP production in the two histamine-responsive cell lines, suggesting that these cell lines express H2 receptors. We conclude that there may be a role for histamine receptor antagonists in melanoma treatment and that further investigation is warranted.

Cell Division↗

Expression of histamine receptors and effect of histamine in the rat carotid body chemoafferent pathway.

Chemosensory information from peripheral arterial oxygen sensors in the carotid body is relayed by petrosal ganglion neurons to the respiratory networks in the medulla oblongata. Biogenic amines, including histamine, released from glomus (type I) cells of the carotid body are considered to be primary transmitters in hypoxic chemosensitivity. Immunocytochemistry at light-and electron-microscopical levels, and RT-PCR, revealed the expression of histamine receptors 1 and 3 as well as histidine decarboxylase in the rat carotid body glomus cells and petrosal ganglion neurons. Histamine receptors 1 and 3, but not histidine decarboxylase, were also observed in the ventrolateral, intermediate and commissural subnuclei of the nucleus tractus solitarii in the medulla oblongata. In order to examine the possible role of histamine in the afferent branch of the respiratory system, we applied histamine receptor 1 and 3 agonists to the carotid body, which caused a mildly increased phrenic nerve activity in a working heart-brainstem preparation. Moreover, microinjection of antagonists of histamine receptors 1 and 3 into the nucleus tractus solitarii caused significant changes in the inspiratory timing and the chemoreceptor response. Our data show that histamine acting via histamine receptors 1 and 3 plays an important neuromodulatory role in the afferent control of chemosensitivity.

Afferent Pathways↗

[Histamine and immune reactions. 1. Histamine receptor-bearing lymphocytes].

Literature review. Mast cells and basophils are included not only in anaphylactic but also in complement activating and cell-mediated immune reactions. A histamine release can be induced via the IgE mechanism, the anaphylatoxins, the histamine releasing activity, and by other reactions. Histamine and several other mediators induce a local inflammation reaction either by a direct action on their target cells or indirectly by the activation of other humoral and/or cellular effector systems. Histamine influences several immune reactions. Here, its influence on histamine receptor-bearing lymphocytes is discussed more in detail. Using in vitro test systems, it has been shown that histamine has a dual effect, it induces a suppression when applied in higher concentrations, while low concentrations are stimulating. In vivo, histamine receptor-bearing lymphocytes have suppressive functions, mediated by H2 receptors. Some preliminary evidence for the inclusion on histamine in the immunoreagulation of patients with several diseases is presented.

Anaphylaxis↗

The H1 receptor agonist 2-(3-chlorophenyl)histamine activates Gi proteins in HL-60 cells through a mechanism that is independent of known histamine receptor subtypes.

In dibutyryl-cAMP-differentiated HL-60 cells, histamine H1 and formyl peptide receptors mediate increases in the cytosolic Ca2+ concentration ([Ca2+]i) via pertussis toxin-sensitive G proteins of the Gi family. We compared the effects of 2-(3-chlorophenyl)-histamine (CPH) [2-[2-(3-chlorophenyl)-1H-imidazol-4-yl] ethanamine], one of the most potent and selective H1 receptor agonists presently available, with those of histamine and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) in these cells. CPH increased [Ca2+]i through Ca2+ mobilization and Ca2+ influx. Unlike histamine-induced rises in [Ca2+]i, those induced by CPH were not desensitized in a homologous manner, and there was no cross-desensitization between CPH and histamine. Like fMLP, CPH activated phospholipases C and D, tyrosine phosphorylation, superoxide anion formation, and azurophilic granule release. The effects of CPH on [Ca2+]i, phospholipase D, and superoxide anion formation were inhibited by pertussis toxin. CPH and fMLP stimulated high affinity GTP hydrolysis by Gi proteins in HL-60 membranes. They also enhanced binding of guanosine-5'-O-(3-thio)triphosphate and GTP azidoanilide to, and cholera toxin-catalyzed ADP-ribosylation of, Gi protein alpha subunits. Histamine receptor antagonists did not inhibit the stimulatory effects of CPH, and CPH did not reduce fMLP binding in HL-60 membranes. Our data suggest that CPH activates Gi proteins in HL-60 cells through a receptor agonist-like mechanism that is, however, independent of known histamine receptor subtypes and formyl peptide receptors. CPH may be an agonist at an as yet unknown histamine receptor subtype or, by analogy with other cationic-amphiphilic substances, may activate G proteins directly. Future studies will have to take into consideration the fact that CPH, in addition to activating H1 receptors, may show other, most unexpected, stimulatory effects on G protein-mediated signal transduction processes.

Calcium↗