Plasma histamine concentrations in evaluation of pediatric mastocytosis.
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Child↗
Biomedical subjects
D D Metcalfe
Publications and source records attributed to D D Metcalfe.
Heterogeneity of mast cells in the tissues of the respiratory tract and other organ systems.
Heterogeneous cytochemical, morphologic, and functional properties have been shown to exist between populations of mast cells in a variety of tissues, or in different histologic subcompartments of the same tissue. This mast cell heterogeneity has important clinical implications for the understanding and treatment of allergic diseases and other conditions where the involvement of mast cells has been postulated. The evidence and implications of mast cell heterogeneity, particularly in the respiratory system, are the topics of this review.
Animals↗
An overview of the controversy concerning questionable manifestations of food allergy.
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Double-Blind Method↗
Mast cell heterogeneity in higher animals: a comparison of the properties of autologous lung and intestinal mast cells from nonhuman primates.
The issue of mast cell heterogeneity has been investigated in nonhuman primates by a comparative examination of lung and intestinal mast cells. These cells were obtained in parallel from the respective tissues of individual monkeys by an identical enzymatic dispersion technique. Mast cells derived from the lungs differed from those derived from the intestine in that the majority of the former cell type could be stained with toluidine blue at pH 4 to 5, whereas the intestinal mast cells in the dispersed preparations required a more acidic pH (less than 1) to display metachromasia. In addition, the lung cells exhibited an increased content of the mast cell mediator histamine. Nonhuman primate lung mast cells were also quantitatively more responsive to an immunologic challenge than their intestinal counterparts in that they released a higher percentage of cellular histamine and generated more leukotriene C4 on stimulation. Considerable inter-animal variation was observed between the magnitude of mediator release from both mast cell types after anaphylactic activation, but evidence for the presence in nonhuman primates of the phenomenon of releasability was not obtained. The responsiveness of both cell types to a range of potential nonimmunologic secretagogues and anti-allergic agents, including compound 48/80, substance P, theophylline, and isoprenaline, was essentially similar. We conclude that mast cell heterogeneity in higher animals may be reflected more by cytochemical rather than by functional differences between mast cell classes.
Animals↗
Mast cell numbers and histamine levels in synovial fluids from patients with diverse arthritides.
Thirty-five synovial fluid (SF) specimens were examined for the presence of mast cells and for their histamine content. Mast cells were seen in SF cells from 27 of 35 fluids, and histamine was measurable in 19 of 34. There was a strong correlation between mast cell number and histamine content. No consistent relationship was found between either the mast cell number or histamine level and the patients' diagnoses, except that the 2 patients with systemic mastocytosis had markedly elevated values for both SF mast cell number and histamine content. SF mast cells from one of the mastocytosis patients were studied for histamine release; significant amounts of histamine were released upon exposure to anti-human IgE, but not compound 48/80. Thus, mast cells similar to those present in connective tissue are frequently present in SF in numbers which correlate with SF histamine levels. These mast cells contain active proteases and are capable of degranulation. Mast cells were consistently present in large numbers in the SF of patients with systemic mastocytosis, but their numbers were highly variable in fluids of patients with other diseases.
Adult↗
The effects of aspartame on mast cells and basophils.
The artificial sweetener aspartame was studied to determine whether it had any direct effects on mast cells and basophils. Aspartame was not shown to be a direct mast cell or basophil secretagogue in vitro, or in vivo as assessed by skin testing. During an acute incubation, aspartame did not affect IgE-mediated histamine release from mast cells. However, mast cells cultured in aspartame for periods of up to 9 days showed enhanced rates of proliferation and decreased responsiveness to releasing stimuli. The effect of aspartame on proliferation of cells in culture could be ascribed to a non-specific enhancing effect of its constituent amino acids.
Animals↗
Mediators of airway inflammation.
Mediators of inflammation can be classified into those that exist preformed in cells and those that are rapidly generated following stimulation. Vasoactive amines, lysosomal enzymes, neuropeptides and proteoglycans are examples of classes of mediators that are synthesized and stored, awaiting the proper stimulus that results in their release. Prostaglandins, leukotrienes, platelet activating factors and free radicals are representative substances that are generated as a result of cell activation. It is now clear that similar inflammatory mediators can be produced by diverse cell types. The exact role of specific mediators of inflammation depends on several factors: the precise stimulus that results in their release or production, the time in the overall inflammatory process when they are produced, and their specific biological effects. Upon stimulation, resident cells such as epithelial cells, mast cells and macrophages are in a position to induce inflammation, whereas cells entering sites of initial injury are able to perpetuate the process. Specificity further depends upon cell surface receptors and the mediators resulting from receptor perturbation. Finally, the most critical question is how inflammation, once induced, is limited by the mammalian system in order to prevent this process from unlimited extension. It would appear that numerous mechanisms which limit injury are brought into play with the induction of inflammation. These mechanisms include degradation of mediators by other mediators, mediator degradation by resident cells, and mediator dilution by tissue fluids. In summary, the role of mediators is extremely complex, involving their innate properties, temporal expression, and inactivation.
Arachidonic Acids↗
Activation of transglutaminase and production of protein-bound gamma-glutamylhistamine in stimulated mouse mast cells.
The identification of transglutaminase in the growth-factor-dependent mouse mast cell line PT18 was accomplished through its characteristic catalytic properties (specificity, calcium dependency, and inhibition by iodoacetamide); and by both immunoprecipitation and Western blot analysis using affinity purified antibody. The enzymatic activity in these cells increased in association with the release of histamine from the cells induced by an IgE-dependent mechanism or by exposure to the ionophores A23187 or Br-x537A. The increase in transglutaminase activity was paralleled by a marked increase in the level of protein-bound gamma-glutamylhistamine, determined in radiolabeled form in mast cells that were either metabolically labeled with [3H]histidine or incubated with [3H]histamine before degranulation. The highest level of bound gamma-glutamylhistamine was found in the immunologically stimulated cells. Enzymatic activity and the gamma-glutamyl derivative were associated primarily with the cells, both before and after stimulation. Separation of gamma-glutamylhistamine in a proteolytic digest of these cells was carried out using a combination of ion exchange chromatography and high performance liquid chromatography. The gamma-glutamyl compound was identified and quantitated through the enzymatic production of histamine with the use of gamma-glutamylamine cyclotransferase, an enzyme specific for the disassembly of gamma-glutamylamines.
Animals↗
Inhibition of IgE-mediated mast cell degranulation by sulphasalazine.
The effect of sulphasalazine on two mast cell populations and human peripheral leukocytes is reported. Sulphasalazine inhibited histamine release from mouse and rat mast cells, but it caused a potentiation of secretion in human peripheral leukocytes. The drug alone did not induce histamine release when administered without an anaphylactic stimulus. The results are discussed in terms of a possible mode of action of sulphasalazine in the treatment of inflammatory bowel disease.
Animals↗
Histamine secretion induced by N-acetyl cysteine.
The mucolytic drug N-acetyl cysteine has been shown to release histamine from cultured mouse mast cells and from human basophils. At neutral pH the release was moderate and non-cytotoxic. If the acidity of the drug was not neutralized, this histamine release was markedly potentiated, but was then associated with a reduction in the viability of the cells. However, the high level of release could not be reproduced by simply exposing the cells to an acidic medium. The results are discussed in terms of a possible mechanism for the adverse reactions sometimes observed during N-acetyl cysteine therapy.
Acetylcysteine↗
Comparison of the therapeutic efficacy of cromolyn sodium with that of combined chlorpheniramine and cimetidine in systemic mastocytosis. Results of a double-blind clinical trial.
Both antihistamines and cromolyn sodium have been suggested for the treatment of systemic mastocytosis. To determine if one drug regimen was superior to the other, eight patients with systemic mastocytosis were admitted to a double-blind, double-crossover study in which the therapeutic efficacy of cromolyn sodium was compared with that of a combination of chlorpheniramine and cimetidine. Response to therapy was assessed by the patients using symptom scores and by the attending physicians during clinic examinations in addition to sequential plasma and urinary histamine determinations. In the six patients who completed the trial, the patient symptom scores and the physician evaluations indicated that there was no advantage of one drug regimen over the other. Plasma and urinary histamine levels, markedly elevated in most of the patients, were not consistently altered by administration of either cromolyn sodium or the combined antihistamines. Thus, cromolyn sodium and the combined antihistamines were indistinguishable when used for the symptomatic treatment of systemic mastocytosis, and neither regimen altered systemic histamine levels.
Adult↗
Evaluation of immediate adverse reactions to foods in adult patients. I. Correlation of demographic, laboratory, and prick skin test data with response to controlled oral food challenge.
Forty-five adult patients, referred to here as the index population, with a history of immediate adverse reactions after food ingestion were evaluated by history, physical examination, laboratory studies, and skin testing. Fifty-six percent of these patients reported adverse reactions to only one food, whereas 84% of the patients reported up to three foods as being capable of eliciting reactions. The average age obtained by history at which adverse reactions began to occur was 19 4/5 yr. The occurrence of these reactions persisted over an average of 14 4/5 yr. Most reactions involved the gastrointestinal tract alone or in combination with the skin or respiratory tract. The most frequently involved foods were shellfish, peanuts, eggs, fish, tomatoes, and walnuts. Twenty-five of the patients participated in oral challenge with the suspected food. The food challenge was positive in 10 patients. Comparison of information obtained by history including personal or family history of any other allergic disease, age of onset of sensitivity, the length of time of suspected sensitivity in years, and the number of foods to which the sensitivity was believed to exist revealed no significant differences between food challenge-positive (FC+) and food challenge-negative (FC-) patients. However, a significant difference in the reaction patterns reported by history in the FC+ and FC- patients was noted in that FC+ patients more often described reactions in which a combination of gastrointestinal, respiratory, and dermatologic symptoms occurred. The complete blood count with differential, blood chemistries, and serum immunoglobulin levels were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Evaluation of immediate adverse reactions to foods in adult patients. II. A detailed analysis of reaction patterns during oral food challenge.
Eighty-three oral food challenges were performed on 25 patients with a history of immediate adverse reaction to foods. Seventy-one food challenges were performed in 24 patients, whereas 12 placebos were administered to nine patients. Of the 71 food challenges observed, 12 were positive in 10 patients. All challenges with placebo were negative. Doses of challenge foods provoking observable reactions ranged from 5 to 100 gm. The clinical signs and symptoms noted on food challenge reproduced those reported by history. Reactions were mild, generally self-limited, and were not accompanied by elevations in urinary histamine. A plasma histamine elevation was observed in one patient. A 10- to 12-mo follow-up survey of nine patients with negative food challenges revealed that six patients had resumed eating the challenge food on a regular basis without experiencing adverse reactions, whereas three patients continued to avoid the challenge food. All 10 patients with positive food challenges continued to avoid the challenge food.
Administration, Oral↗
Failure of sulfites to produce clinical responses in patients with systemic mastocytosis or recurrent anaphylaxis: results of a single-blind study.
Although sulfite sensitivity can precipitate asthma in a subpopulation of subjects with asthma, its role in precipitating anaphylaxis or as a nonspecific mast cell degranulator in systemic mastocytosis has not been examined. To evaluate critically the importance of sulfites in these diseases, eight patients with systemic mastocytosis and 25 patients with unexplained, recurrent anaphylaxis were challenged in a single-blind fashion; sodium bisulfite in capsules was administered in increasing doses of 1, 5, 10, 25, 50, 100, and 200 mg every 30 minutes. On separate occasions a liquid suspension of 200 mg of sodium bisulfite was administered to one patient with systemic mastocytosis and nine patients with anaphylaxis. Vital signs, pulmonary function tests, plasma histamine levels, and clinical reactions were monitored. There were no observable responses in either the mastocytosis group or in 23 of 25 patients in the anaphylaxis group. Two patients in the anaphylaxis group with initial positive challenges had similar symptoms on subsequent placebo challenge. One subject with asthma and with a history suggestive of sulfite sensitivity responded to oral challenge with 5 mg of sodium bisulfite and 100 micrograms of sodium bisulfite intradermally with a dramatic reduction in FEV, requiring treatment with bronchodilators. A comparison of baseline plasma histamine levels with those obtained after the sulfite challenge procedure in each category demonstrated a significant rise (p less than 0.05) in the systemic mastocytosis group. The overall level of significance determined by applying paired sample t tests to the histamine data from all subjects was p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Interactions between mast cells, fibroblasts and connective tissue components.
It has long been recognized that mast cells occur throughout connective tissues. Histologic studies have revealed that such cells release their granules into the surrounding environment upon exposure to both immunologic and nonimmunologic stimuli. By microscopy these extracellular granules appeared to be phagocytosed by fibroblasts and by blood-borne phagocytic cells as they entered the site of mast cell degranulation. Such in vivo observations led to the suggestion that mast cells both altered connective tissue components and influenced fibroblast function through these discharged granules. Recent in vitro studies using cultured fibroblasts and isolated mast cells and mast cell granules have confirmed both these hypotheses. In addition, such studies have also documented that fibroblasts degrade ingested mast cell granules. Such studies document that a number of critical interactions may occur between mast cells and connective tissue components.
Animals↗
Unique features of human basophilic granulocytes developed in in vitro culture.
Human basophilic granulocytes were obtained in suspension culture of mononuclear cells from umbilical cord blood. Precursors of basophils in the cord blood are nonadherent cells and bear neither surface Ig nor T cell marker. Cultured basophils contain chondroitin-4-sulfate proteoglycan, 1.74 micrograms histamine per 10(6) cells in average, and bear 120,000-380,000 IgE receptors per cell. The IgE receptor molecule has a molecular weight of approximately 64,000 daltons. Human, rat and mouse IgE bind to the receptors with comparable high affinity and passively sensitize the cells for mediator release. Challenge of sensitized basophils with anti-IgE resulted in stimulation of phospholipid methylation, 45Ca uptake, release of both histamine and free arachidonic acid, and enhancement of phosphatidylinositol (PI) turnover. Evidence was obtained that the activation of membrane-associated proteolytic enzyme and methyltransferases is involved in subsequent IgE-mediated biochemical cascades such as PI turnover, Ca2+ uptake and mediator release.
Antibodies, Anti-Idiotypic↗
Oligoclonal immunoglobulins in mastocytosis.
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Adult↗