Increase In Histamine Concentration Research Articles

Factors Influencing Basophilic Differentiation of HL-60 Cells

Lineage-specific hematopoietins apparently act in concert with multipotent factors in an orderly sequence of growth and differentiation. We have used the human acute promyelocytic leukemia cell line HL-60 to examine basophilic differentiation, using radioenzymatic assay of histamine content as an end point. Recombinant human interleukin 1 (rhIL-1), rhIL-2, rhIL-4, and recombinant human alpha and gamma interferons did not stimulate basophilic differentiation either in the presence or absence of sodium butyrate, an important cofactor for induction of differentiation. In contrast, rhG-CSF (granulocyte colony-stimulating factor), rhGM (granulocyte-macrophage) CSF, rhIL-3, rhIL-5, nerve growth factor, conditioned medium (CM) from the hairy T cell leukemic line Mo, and nasal polyp epithelial CM stimulated significant increases in histamine content in HL-60 cells at day 5 in vitro. GM-CSF did not account for all of the basophilic differentiating activity in Mo-CM. The data suggest that a unique, lineage-specific, basophilic cell differentiation factor is produced by T cells and point to the possible diagnostic and therapeutic relevance of in situ hematopoietic mechanisms in human respiratory disease.

Changes in plasma histamine during orthotopic liver transplantation in the pig

Hypotension and cardiac arrhythmia are commonly seen during liver transplantation both in man and in experimental animals. The cardiovascular changes may be explained by release of vasoactive substances, e.g. histamine, into the systemic circulation. Abdominal operations are followed by an increased histamine concentration in portal blood. If the liver clears excess histamine from the splanchnic system, an increased histamine concentration should not be found in the systemic circulation. We measured plasma histamine in peripheral arterial blood, blood from the right atrium and portal blood in different phase of liver transplantation in ten pigs. Histamine concentration increased in the portal vein in the anhepatic phase (basal 15.85 pmol/ml to 34.67 pmol/ml, median, p less than 0.05) but no changes were found in arterial or right atrium samples. Venous and later arterial revascularisation were not followed by any changes in histamine concentration in arteria and right atrium samples. We conclude that the transplanted liver can eliminate splanchnic histamine and that histamine is unlikely to be involved in the cardiovascular changes which are seen after revascularisation of the liver.

Combination of localized heat urticaria and cold urticaria. Release of histamine in suction blisters and successful treatment of heat urticaria with doxepin

Summary Two female patients with a rare combination of localized heat urticaria and cold urticaria are described. One patient had localized heat urticaria combined with delayed cold urticaria and the other patient had localized heat urticaria in combination with idiopathic (primary acquired) cold urticaria. Increased histamine concentration was measured in suction blister fluid samples collected immediately after the heal challenge in both patients. Doxepin effectively suppressed the whealing response on the heat challenged skin. These results suggest that histamine is the main mediator in heat urticaria reactions.

Histamine generation by bacteria in sputum of patients with chronic obstructive airway disease

Previous investigations have demonstrated high histamine concentrations in the sputum of patients with chronic obstructive airway disease (COAD). A possible histamine generation by bacteria has been discussed. In the present work, histamine concentrations in native and incubated sputum of patients with COAD were determined. Histamine was assayed fluorimetrically after separation by HPLC. Histamine concentration in native sputum amounted to 10-1140 ng/ml. After 72 h incubation at 37 degrees C 100-20,700 ng/ml histamine was detected. A mean 26-fold increase in histamine content was observed. Heating of the sputum almost completely prevented the rise in histamine concentration during incubation. The same effect was achieved by adding an antibiotic to the sputum before incubation. Histamine content in sputum of patients with COAD decreased considerably after therapy with the antibiotic doxycycline. Histamine formation by bacteria may account considerably for the histamine concentration in sputum of patients with COAD.

Changes in Leucocyte Numbers without Diapedesis in Rats Given Platelet-Activating Factor (PAF-Acether)

Changes occurring in the blood and the peritoneal cavity following the intraperitoneal injection of platelet-activating factor (PAF-acether) into rats were compared with those when antigen was injected intraperitoneally into actively sensitised rats. A blood eosinophilia had been produced in the rats by an intravenous injection of Sephadex G200 6 days before either challenge. 5 min after PAF-acether, the total number of cells in the peritoneal washings had decreased and the concentration of extravasated dye-labelled plasma protein had increased with no change in histamine levels. On the other hand, antigen at this time produced nor only a decrease in cells and an increase in dye but also an increase in histamine concentration. Only antigen produced a cellular infiltration into the peritoneal cavity with an increase in numbers of neutrophils in the peritoneal washings at 4 h and of mononuclear cells and eosinophils at 24 h. In the blood at 4 h after either challenge, there was a neutrophilia and an eosinopenia. When PAF-acether and antigen were injected together into actively sensitised rats, leucocyte counts in the peritoneal washings increased by a similar amount, both at 4 and 24 h, as those in rats given antigen alone.

Hyperplasia of the mesenterial windows precedes that of the small gut in the streptozotocin-diabetic rat.

Hyperplastic growth of the mesenterial windows abutting the small gut occurs in lactating rats (Bergström and Norrby 1988) and chronically diabetic rats (Norrby et al. 1983). In the present study, early events in the mesenterial windows and the small gut in streptozotocin-diabetic rats were examined. The area of the mesenterial windows had already increased significantly on day 1 and hyperplasia in terms of increased DNA content, as well as an increase in histamine content (a mast-cell marker), was established from day 2 of diabetes. The increase in total mesenterial window content of DNA, histamine and protein was roughly linear and parallel from day 2 to day 19. The small-gut circumference increased transiently on day 1, but the small-gut mucosal volume was unaffected on days 1 and 2. The small-gut wet weight increased significantly from day 5, whereas elongation was not observed until day 19. The difference in time between the appearance of hyperplasia and the growth of the mesenterial windows and their adjoining gut and the rate with which the hyperplasia proceeds in the two tissues indicate that the regulatory mechanisms of early hyperplastic growth in these tissues are not identical. The factor(s) causing mesenterial window growth and hyperplasia is/are as yet unknown.

Carboxypeptidase A in mouse mast cells. Identification, characterization, and use as a differentiation marker.

By using a conventional spectrophotometric assay with hippuryl-L-phenylalanine as the substrate, 10(6) BALB/c mouse serosal mast cells possessed 1.5 +/- 0.43 U (mean +/- SE, n = 5, range = 0.48 to 2.5) of carboxypeptidase A activity, while T cell factor-dependent, mouse bone marrow-derived mast cells (BMMC) had barely detectable levels of 0.01 +/- 0.001 U/10(6) cells (mean +/- SE, n = 3). In order to characterize the carboxypeptidase A present in the BMMC, a sensitive assay was developed that used angiotensin I as the substrate and reverse phase-high performance liquid chromatography to separate and quantify production of the cleavage product des-leu-angiotensin I. Using this assay, mouse BMMC carboxypeptidase A had a neutral to basic pH optimum and hydrolyzed angiotensin I with a Km of 0.78 mM. The antigen-induced net percent release of carboxypeptidase A from IgE-sensitized BMMC was proportional to that of the secretory granule component beta-hexosaminidase which indicates a secretory granule location for the exopeptidase. As defined by exclusion during Sepharose CL-2B chromatography, carboxypeptidase A was exocytosed as a greater than 1 X 10(7) m.w. complex bound to proteoglycans. Because BMMC cocultured with mouse skin-derived 3T3 fibroblasts are known to undergo an increase in histamine content and biosynthesis of 35S-labeled heparin proteoglycans, carboxypeptidase A activity was measured during BMMC/fibroblast coculture for 0 to 28 days. The carboxypeptidase A activity increased progressively during 28 days of co-culture from 0.004 +/- 0.002 U/10(6) starting BMMC (mean +/- SE, n = 3) to 0.36 +/- 0.10 U/10(6) co-cultured mast cells. These findings indicate that carboxypeptidase A, a neutral protease, is exocytosed from the secretory granules of mouse mast cells bound to proteoglycan and is increased during the in vitro differentiation of mouse BMMC from mucosal-like mast cells to serosal-like mast cells.

Role of mast cells in the pathogenesis of hypersensitivity pneumonitis.

To examine the possibility that mast cells have a central role in the pathogenesis of hypersensitivity pneumonitis, 20 patients with this disease were studied with the aim of seeking evidence for mast cell degranulation. The number of mast cells recovered by bronchoalveolar lavage from patients with hypersensitivity pneumonitis was more than 1,000 times greater than those recovered from normal individuals. Furthermore, discontinuation of antigen exposure resulted in an increase in the number of mast cells observed, consistent with the possibility that antigen exposure had induced mast cell degranulation. Cessation of antigen exposure also resulted in a rapid decrease in the number of neutrophils and eosinophils recovered by lavage, followed by an increase in the number of T8+ T lymphocytes present. In each case the time course of the changes was consistent with the possibility that mast cell degranulation had been important in regulating the number of the immune and inflammatory cells present in the lung. Histamine was present in lavage fluid supernatant from patients with hypersensitivity pneumonitis. The amount of histamine present was, however, closely correlated with the number of mast cells present and not with the interval since last antigen exposure. Delay in separating cells from lavage fluid supernatant resulted in an increase in histamine content. These results suggest that the free histamine in lavage fluid resulted from the degranulation of mast cells induced by the lavage procedure as histamine released in vivo has a short half life. We suggest that hypersensitivity pneumonitis results from a "late phase reaction" initiated by antigen induced mast cell degranulation.

Induction of histidine decarboxylase by dexamethasone in mastocytoma P-815 cells

Dexamethasone at a concentration as low as 10 nM significantly increased both the histamine content and histidine decarboxylase activity of cultured mastocytoma P-815 cells. Both effects were clearly seen using several glucocorticoids, which were as effective as dexamethasone. In contrast to that of histamine, the serotonin level of mastocytoma P-815 cells was decreased by treatment with dexamethasone. The dexamethasone-induced increases in histamine content and histidine decarboxylase activity were completely suppressed by the addition of cycloheximide and actinomycin D. Mastocytoma P-815 cells were found to possess binding sites for [ 3H]dexamethasone in the cytosol ( K d = 15.7 nM) and the nuclei ( K d = 1.26 nM). These results show that glucocorticoids significantly stimulate de novo synthesis of histidine decarboxylase.

Quantitative skin prick testing

Dose-response curves of histamine- and allergen-induced wheal areas were evaluated in seven normals (defined as negative skin prick test (SPT) to inhalant allergens and no clinical signs of allergy), seven latent allergics (positive SPT without allergic symptoms), and 20 manifest allergics (positive SPT and allergic symptoms). Three concentrations of histamine HCl (1, 10 and 100 mg/ml) and three 10-fold concentrations of nine inhalant allergens (birch, timothy, mugwort, horse, dog, cat, house dust mite, Cladosporium and Alternaria) in concentrations 1,000 10,000 and 100,000 BU/ml were used and linear regression was performed on the skin reactions. Only tests with an SD% less than 40%, a log slope greater than 0.1, and a correlation coefficient greater than 0.95 were accepted. In normals a significantly higher concentration of histamine was needed to elicit a wheal reaction of 2 mm2 (end-point) compared with allergics. Likewise, normals had a significantly higher slope i.e. steeper dose-response curve of histamine than manifest allergics. The slope of the allergen-induced wheal area was significantly higher than the histamine slope. No relation between corresponding slope of histamine and allergens was found (Rho = 0.15). The skin sensitivity equivalent to histamine calculated as the allergen concentration eliciting a wheal equal to histamine showed a median increase of 5-6 fold in allergen concentration by a 10-fold increase of histamine concentration. The highest correlation between the wheal area of a single allergen concentration and the skin sensitivity was found for allergen concentration 100,000 BU.(ABSTRACT TRUNCATED AT 250 WORDS)

EFFECTS OF TUBOCURARINE ON PLASMA HISTAMINE CONCENTRATION IN THE RAT: Correlation with the Release of Histamine from Isolated Mast Cells

The administration of tubocurarine i.v. in man produces hypotension, probably as a result of the release of histamine. The mechanisms involved in this action of tubocurarine on the plasma histamine concentration in rats, and on the isolated peritoneal mast cells were investigated. I.v. injections of tubocurarine (greater than 5 mg kg-1; corresponds to tubocurarine 4 X 10(-4) mol litre-1 in the plasma of the rats) evoked a phasic increase in plasma histamine concentration. In vitro studies showed that tubocurarine 4 X 10(-4) mol litre-1 released about 20% of the histamine contained in the isolated mast cells. Treatment of the mast cells with carbachol or atropine evoked no histamine release, nor did it modify the tubocurarine-induced release of histamine. These results suggest that the increased histamine concentrations in the plasma are attributable to an action of tubocurarine on the mast cells which is not mediated through the acetylcholine receptors distributed on these cells.

Coculture of interleukin 3-dependent mouse mast cells with fibroblasts results in a phenotypic change of the mast cells.

The heparin-containing mast cells that reside in the connective tissue of the mouse, but not the chondroitin sulfate-containing mast cells in the gastrointestinal mucosa, stain with safranin when exposed to alcian blue/safranin. Mouse bone marrow-derived mast cells (BMMC), the probable in vitro counterparts of in vivo mucosal mast cells, were cultured for 14 days with mouse skin-derived 3T3 fibroblasts in RPMI 1640 medium containing 10% fetal calf serum and 50% WEHI-3 conditioned medium. Although the BMMC adhered to the fibroblast monolayer, they continued to divide, probably due to the presence of interleukin 3 in the conditioned medium. The mast cells remained viable throughout the period of coculture, since they failed to release lactate dehydrogenase and because they increased their histamine content approximately 15-fold. After 12-14 days of coculture, greater than 50% of the BMMC changed histochemically to become safranin+; 30-40% of the 35S-labeled glycosaminoglycans on the proteoglycans synthesized by these cocultured mast cells were heparin, whereas heparin was not detected in the initial BMMC. In the absence of WEHI-3 conditioned medium, BMMC adhered to the fibroblast monolayer, and after 8 days of coculture, the number of mast cells did not change and their histamine content remained the same. However, these mast cells also became safranin+ and synthesized 40% heparin glycosaminoglycans. Thus, coculture of BMMC with fibroblasts induces a phenotypic change so that the resulting mast cells stain safranin+ and synthesize heparin proteoglycans, whereas the presence of WEHI-3 conditioned medium stimulates proliferation and an increase in histamine content.

Histamine is released from skin by substance P but does not act as the final vasodilator in the axon reflex

We have explored in man the hypothesis that histamine released from dermal mast cells by neurotransmitters from afferent nerves contributes to vasodilatation of the axon reflex. The ability of substance P to release histamine from human skin in vivo, and the effects of a histamine H1-receptor antagonist on capsaicin-induced axon reflex flares were studied. Intradermal injections of substance P (50 pmol) produced a weal and flare response which was associated with increased histamine concentration in blood draining the site (mean plasma histamine concentration before injection 0.17 +/- 0.02 ng ml-1 (+/- s.e.mean), concentration one minute after injection 1.26 +/- 0.28 ng ml-1, n = 6). Terfenadine, an H1-receptor antagonist, had no effect on the flare response to intradermal injection of capsaicin at a dose which inhibited by more than 60% the flare response to exogenous histamine and to histamine released from dermal mast cells by substance P. Substance P releases histamine from human skin in vivo. However, whatever the nature of the neurotransmitter released from afferent nerves during the axon reflex, it does not produce vasodilatation through release of histamine from dermal mast cells. Histamine may still contribute to the flare by initiation of the reflex.

ATRACURIUM: CLINICAL STRATEGIES FOR PREVENTING HISTAMINE RELEASE AND ATTENUATING THE HAEMODYNAMIC RESPONSE

This study was designed to determine the effects of a rapid bolus dose of atracurium 0.6 mg kg-1 on arterial pressure, heart rate and plasma histamine concentration (n = 9), and to compare these values with those obtained by (a) giving the same dose of atracurium slowly (over 75 s) (n = 9), or (b) pre-treating with H1- and H2- antagonists (n = 9). The rapid (5-s) bolus dose of atracurium i.v. resulted in a significant increase in plasma histamine concentration (P less than 0.05) and was associated with a decrease in mean arterial pressure and an increase in heart rate. Administering the same dose of atracurium slowly (over 75 s) prevented the increase in plasma histamine concentration, and abolished the subsequent haemodynamic response. Pretreatment with cimetidine 4 mg kg-1 i.v. and chlorpheniramine 0.1 mg kg-1 i.v. abolished the haemodynamic response despite a moderate increase in histamine concentration (0.1 greater than P greater than 0.05).

Change of hepatic histamine content during hepatic fibrosis

Hepatic function was studied by measuring the time courses of several variables in blood and liver using a chronic liver-injury model produced by administering CCl 4 consecutively for 12 weeks in rats. A marked increase in liver histamine content occurred after 10 weeks of treatment with CCl 4. At weeks 10 and 12, liver histamine levels in the CCl 4-treated group were 1.95 and 4.61 times higher, respectively, than in the control group. This change in liver histamine content appeared after that in other variables such as glutamic pyruvic transaminase, alkaline phosphatase, and white blood cells, but it corresponded to a change in liver hydroxyproline. Increased mast cells were seen in fibrotic foci around Glisson's sheath by microscopic morphological observation of the liver 12 weeks after treatment with CCl 4. The histamine concentration in plasma tended to decrease after CCl 4 treatment, and at week 12 the decrease was statistically significant compared with control. The liver activities of histamine-metabolizing enzymes, histamine- N-methyltransferase and histaminase, decreased to 1 3.4 and 1 6.0 times those of the nontreated group, respectively, 12 weeks after treatment with CCl 4, whereas blood histaminase increased about 9.2 times. The increase in histamine content in injured liver was presumedly derived from the increase in mast cells in the inflamed area of the liver; also, the deficiency of histaminemetabolizing enzymes in liver might have caused the high histamine content in the liver. On the other hand, the decrease in plasma histamine concentration might have occurred as a consequence of the enzyme leakage from hepatocytes that accompanied the breakdown of hepatocytes by CCl 4 and thus, of the histamine metabolism in blood by the leaked enzymes. The same kind of experiment was performed using a dimethylnitrosamine-induced liver injury model in rats. The increase of hydroxyproline in the liver occurred 11 days after that of histamine content in liver. These results suggest the possibility that increased histamine in the liver may participate in the biosynthesis of collagen.

Immunologic studies in allergen-induced late-phase asthmatic reactions

We have measured plasma histamine, serum neutrophil chemotactic activity (NCA) and complement (C3 and C4) over a 24-hour period in patients experiencing either early- and late-phase (dual) or single early asthmatic reactions to inhaled allergens. There was a significant biphasic elevation in plasma histamine, which paralleled the fall in forced expiratory volume in 1 sec in 10 patients with dual responses, whereas in seven subjects with single early reactions, only a single early increase in histamine concentrations was observed. In general, in the individual subjects, the changes in plasma histamine paralleled both the elevations in serum NCA and the decreases in forced expiratory volume in 1 sec. By gel filtration on Sephacryl S-400, anion exchange chromatography on DEAE Sephacel, and chromatofocusing with Polybuffer Exchanger 94, the major NCA of both the early and the late reactions was associated with proteins having an estimated molecular size of 600,000 daltons, an elution from DEAE Sephacel at 0.15M to 0.30M of NaCl (pH 8.1), and a pI of approximately 6.5. There were no appreciable changes in serum C3 and C4 up to 24 hr after challenge in subjects with late-hase responses. The patterns of asthmatic response were not related to either the total or allergen-specific serum IgE or IgG 4 concentrations. These results support the view that mediators of hypersensitivity participate in late-phase as well as early asthmatic reactions.

Mediator release in local heat urticaria

We described the sixteenth reported case of local heat urticaria, in a 59-yr-old woman with erythema and angioedema upon contact with hot water or outdoor heat exposure. Immersing her hand in 39° to 40° C heated water resulted in an erythematous, angioedematous response sharply demarcated by the line of immersion and was associated with immediate increases in histamine concentration (18 to 135 ng/ml) and high molecular weight neutrophil chemotactic activity (two to five times prechallenge levels) in venous blood draining the challenge site. We suggest that the local heat urticarial response in this woman was a form of physical urticaria associated with release of mast cell-derived mediators, akin to cold and cholinergic urticaria.

Human rotaviruses increase serotonin release from human intestinal carcinoid cells cultured in vitro

Summary Serotonin and histamine putatively affect the onset of some diarrheic syndromes. We have studied the effects of human rotavirus infection on histamine and serotonin release from human intestinal carcinoide cell culture. The viral infection triggered a seven-fold increase in serotonin concentration and a two-fold increase in histamine concentration in culture supernatants. These results suggest that serotonin production is implicated in the pathophysiology of rotavirus-induced diarrhea.

Increase in histamine concentrations in discrete hypothalamic nuclei of spontaneously hypertensive rats

Histamine meets many of the criteria which must be satisfied in order to consider a compound as a neurotransmitter in the central nervous system (CNS). It is localized in synaptosomes after subcellular fractionation of brain tissue is. Discrete histaminergic pathways have been described in the brain 10. Endogenous histamine can be released from brain slices by depolarizing the nerve cells with potassium as. Iontophoresis of histamine modifies the action potentials of cerebral neurons 25. When injected intraventricularly 27 or directly into discrete brain areas 12, histamine has potent effects on neuronal activity. In addition, histamine receptors 7 and a histamine-sensitive adenylate cyclase la have recently been characterized in the brain. Pharmacological evidence indicates that histamine has centrally mediated effects on blood pressure2,14,as, 37. These observations suggest that endogenous brain histamine could play a role in the regulation of blood pressure or in the pathogenesis of hypertension. Selective changes in catecholamine metabolism, discretely localized to a few nuclei and areas of the brain, had been found in several models of hypertension 2s-a0. A similar situation could be envisioned for other putative neurotransmitters such as histamine. We have attempted the quantitation of endogenous histamine levels in those discrete brain areas which are part of the principal central pathways regulating cardiovascular functions in mammals. The study was conducted at two stages of the development of the genetic hypertension using young (4 weeks old) and adult (12 weeks old) spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats, WKY)ZL These ages were selected for their difference in manifested high blood pressure and because there are age-specific changes in catecholamine metabolism in similar brain structures29, so.

Ontogenesis and regional distribution of histamine and histamine-N-methyltransferase in the guinea pig brain.

Abstract—The ontogenetic development and the regional distribution of histamine (HA) and histamine‐N‐methyltransferase (HMT, EC 2.1.1.8) in guinea pig brain and pituitary gland were studied. The samples were taken every fourth day beginning on the 28th foetal day. The HA concentration in the brains of the youngest foetuses was almost undetectable. A significant increase in HA concentrations occurred between days 40 and 44, which coincides with the period of rapid growth of nerve cell processes in this species. After this, a steep increase continued to the end of gestation in the hypothalamus, and to a lesser degree in the medulla‐midbrain and in the forebrain. In all parts of the brain the adult HA levels were reached by the time of birth. The HMT activity increased 15‐fold from the 28th foetal day to the adult and reached ca. 80% of the adult activity by the time of birth. The HMT activity developed earlier in the midbrain than in the forebrain or in the cerebellum, but after the birth the regional distribution of HMT was fairly even. In the pituitary gland the HA concentration and HMT activity increased hundredfold and tenfold, respectively.The developmental patterns of HA and HMT in the guinea pig brain give support to the concept that HA might be a neurotransmitter in the brain.