Ambroxol inhibits histamine release from human adenoidal mast cells

Inflammation Research -     

The effects of heavy metal ions (Cd2+, Hg2+, Pb2+, Bi3+) on histamine release from human adenoidal and cutaneous mast cells

The influence of lead (Pb[CH₃COO]₂), mercury (HgCl₂), cadmium (CdSO₄) and bismuth (BiO[ClO₄]) on the spontaneous and stimulated histamine release from human adenoidal and cutaneous mast cells was tested in the concentration range 10^–8–10^–4 M. Lead displayed a bell shaped dose-response relationship in adenoidal mast cells with a maximum at 10^–6 M whereas in cutaneous cells only the spontaneous release was slightly enhanced at 10^–4 M. Mercury induced a presumably toxic histamine release in adenoidal and cutaneous mast cells at 10^–4 M. Cadmium increased the histamine release in adenoidal cells at 10^–4 M but in cutaneous cells only the stimulated release (10^–8–10^–5 M) was affected. Bismuth inhibited the histamine release at 10^–4 M in the adenoidal mast cells only. In conclusion, human adenoidal and cutaneous mast cells are affected differently by metal ions.     

The effects of prostaglandins of the E and I type on histamine release from human adenoidal mast cells

PgE₁ (10^–8–10^–6 M) inhibited dose dependently the Con A-induced histamine release from human adenoidal mast cells. Out of two stable PgI analogues tested, EL 784 had a slight inhibitory effect at 10^–10 M, and SE 63 at 10^–4 M. PgI₂ itself was ineffective.     

Gastrin induces histamine release from human cutaneous mast cells

Physiologic concentrations of human gastrin I (G17) and a synthetic analog of the carboxy-terminal region of gastrin, pentagastrin, provoked a dose-related release of histamine from human cutaneous mast cells in vitro. The N-terminal tridecapeptide portion of gastrin (G1-13) neither stimulated histamine release nor blocked the action of G17. In vivo correlation studies demonstrated that low concentrations (10(-12)M to 10(-10)M) of G17 or pentagastrin administered intradermally provoked a modest but definite wheal-and-flare response in four out of six normal subjects and a more marked, dose-related response in a patient with mastocytosis. These results indicate that physiologic concentrations of gastrin can stimulate mediator release from human cutaneous mast cells. We propose that this response may be mediated through receptors recognizing the carboxy-terminal region of the gastrin molecule. The possible role of gastrin-induced human mast cell-mediator release should be considered in the assessment of allergic disorders and in experimental models investigating mast cell function.     

The effects of adenosine and of some adenosine analogues on the concanavalin A- or acetylcholine-induced histamine release from human adenoidal mast cells

Histamine release induced by concanavalin A (Con A) or acetylcholine is enhanced by adenosine or the adenosine analogues PIA and NECA. The enhancement is not affected by preincubation with adenosine deaminase.The degree of the Con A-induced histamine release decreases with increasing incubation time. Under these conditions, the enhancing effect of adenosine on histamine release is either abolished or even reversed to inhibition.     

The effects of metoclopramide and cloxacepride on human mast cells from adenoidal tissues

Cloxacepride is an amide of the dopamine antagonist metoclopramide and has been reported to possess oral antiallergic properties in the rat PCA model. Both substances have now been tested in isolated mast cell preparations from human adenoidal tissues to determine whether any therapeutic antiallergic potential in man could be expected.Metoclopramide at concentrations 10^–5–10^–3 M had no inhibitory effect but instead enhanced Con A-induced histamine release at concentrations greater than 10^–4 M. Cloxacepride at concentrations 10^–5–10^–4 M significantly inhibited Con A-induced histamine release. This inhibitory effect was not diminished by increasing the preincubation time for up to 30 min. In contrast, cloxacepride concentrations greater than 4×10^–5 M caused a substantial histamine release. This effect could not be alleviated by an increase in the number of mast cells per sample. These results then suggest a very narrow range of therapeutic potential for cloxacepride.     

Platelet activating factor does not release histamine from human dispersed cutaneous mast cells

Histamine H1-antagonists inhibit the weal-and-flare responses to the intradermal injection of platelet activating factor (PAF) in humans, and PAF response is reduced in histamine-depleted skin sites. This indicates that mast cell histamine release is likely to be the mechanism of this response. We have therefore studied the interaction of PAF with cutaneous mast cells by observing whether it releases histamine directly from human dispersed foreskin mast cells, potentiates the activity of known mast cell stimulants or liberates histamine releasing factors (HRFs) from human platelets and leucocytes to release mast cell histamine by an indirect mechanism. At a concentration of 100 microM both PAF C18 and PAF C16 caused near maximal release (83.5 +/- 4.3% and 88.2 +/- 4.5% respectively) of the total histamine content of the cell. This release was not inhibited in the absence of extracellular Ca2+, by the lack of metabolic energy or in the presence of the PAF antagonists WEB 2086 (100 nM-3 microM) or BN 52021 (100 nM-10 microM). These results indicate a cytotoxic mechanism of histamine release by PAF 100 microM. PAF (10 nM-1 microM) failed to potentiate the mast cell-stimulating activity of anti-IgE, calcium ionophore A23187 or substance P and it did not induce the release of HRFs for skin mast cells when incubated with platelets and leucocytes in concentrations up to 1 microM.     

The influence of H1-, H2- and H3-receptors on the spontaneous and ConA induced histamine release from human adenoidal mast cells

The effects of the H₃-agonist R--methylhistamine (R--MeHA) and the H₃-antagonist thioperamide on the spontaneous and concanavalin A (ConA) induced histamine release from human mast cells were tested and compared with the effect of some H₁- and H₂-receptor active substances. R--MeHA (10^–9–10^–7 M) exerted no effect on histamine release whereas thioperamide increased the spontaneous release at 10^–6–10^–4 M but inhibited the ConA induced release in a narrow concentration range (10^–6–10^–5 M). This enhancement might be taken as an indication of the existence of H₃-receptor dependent autoregulation although presently other mechanism cannot be excluded.     

人肥大细胞的IgE依赖性组胺和类胰蛋白酶分泌

目的　利用人结肠组织的肥大细胞和肥大细胞激活的体外研究系统评价人肥大细胞释放类胰蛋白酶和组胺的能力及其机制。方法　经酶悬浮的人结肠肥大细胞与抗IgE抗体共同培养后记录浓度相关曲线和时间关系曲线。类胰蛋白酶用酶联免疫吸附试验的方法测量 ,而组胺则由一种以玻璃纤维为基础的荧光比色法测量。结果　抗IgE抗体可引起浓度相关性的组胺和类胰蛋白酶释放 ,最大组胺和类胰蛋白酶分泌量分别比基础分泌量超出 2 .7和 2 .5倍以上。抗IgE抗体的作用从加样后 10s开始 ,6min后达高峰并至少持续 15min。百日咳毒素和代谢抑制剂能够分别抑制抗IgE抗体引起的组胺和类胰蛋白酶释放。百日咳毒素还能够减少自发性类胰蛋白酶释放。结论　人结肠肥大细胞在受到抗IgE抗体刺激时具有平行释放类胰蛋白酶和组胺的能力 ,这个过程与肥大细胞膜G蛋白偶联受体的激活有关 ,并消耗能量。肥大细胞自发性释放组胺和类胰蛋白酶的功能可能是通过不同的机制实现的。     

Movement of calcium ions and release of histamine from rat mast cells

Rat mast cells were stimulated for histamine release in a medium containing radioactive calcium, by band 2 protein (B2) and compound 48/80. It was found that a significant amount of extracellular calcium was taken up by the stimulated cells. When the histamine release process was divided into two stages by activating the cells at 0 degrees C and then washing them prior to suspending them in Tyrode's solution at 37 degrees C, it was found that calcium uptake by the cells took place at the release stage. This suggests that calcium entry into the cells occurs subsequent to the activation stage. Inhibition of histamine release by 2-deoxyglucose (2-DG) and 2,4-dinitrophenol (DNP) also inhibited the calcium influx into the cells. The present studies also suggest that calcium does not diffuse into the cells as a result of degranulation. These findings have been discussed in relation to the mobilization of intracellular calcium.     

The effects of food additives and aflatoxin B1 on histamine release from human mast cells

The effects of the food additives tartrazine, biphenyl, sorbic acid and the mycotoxin contaminant aflatoxin B₁ were studied in mechanically isolated human adenoidal mast cells. Tartrazine inhibited the spontaneous histamine release in the concentration range of 10^–9 to 10^–5 M and the concanavalin A (Con A)-induced histamine release dose-dependently at 10^–11–10^–5 M [10.3%–31.6%]. Biphenyl [10^–9–10^–6 M] neither influenced the spontaneous nor the stimulated histamine release. Sorbic acid [10^–7–10^–4 M] slightly inhibited the Con A-induced release at the highest concentration tested. Aflatoxin B₁ [10^–10–10^–7 M] did not influence mediator release after a preincubation time of 5 min. Extension of the preincubation period inhibited the histamine release slightly. In summary, none of the tested substances enhanced histamine release from human adenoidal mast cells. Tartrazine even had an inhibitory effect.     

Characteristics of histamine release from cultured human mast cells

Background The mtist cell is one of the important cells In the pathogenesis of allergic disorders. However, isolating human mast cells is a laborious procedure. Recently, cultured human mast cells raised from umbilical cord blood cells have become available. It is necessary to examine whether these cells are useful in investigating the role of mast cells in human diseases. Objective The phenotype of mast cells depends on their anatomical sites. To examine which phetiotype of mast cells these cultured mast cells most closely resemble, their ability to release was investigated. Methods The mast cells were raised from human umbilical cord blood cells in the presence of stem cell factor and interIeukin-6. To determine the mast cell subtypes, the mast cells were immunocytochemically stained for tryptase and chymase. The cultured mast cells were then stimulated with various secretagogues, and histamine release was measured by a fluorometric technique using high-performance liquid chromatography. Results The immunocytochemical staining for mast cell proteases revealed that virtually all cells contained tryptase, the definitive marker of mast cells, and that about a quarter of the cells contained chymase. Anti-TgE effectively stimulated these mast cells to release histamine in a dose-dependent, lime-dependent manner. The release was completed in about 30 min. One of the non-specific stimuli, calcium ionophore A23I87. also induced histamine release in a dose-dependent, time-dependent manner. In contrast, compound 48/80 and substance P failed to induce histamine release from these cells. Conclusion Cultured human mast cells resemble lung mast cells in their ability to release histamine. They will help in studying the functional properties of human mast cells and may contribute to clarifying the pathophysiology of human allergic diseases.     

Histamine release from human adenoidal and mesenteric mast cells induced by bacterial antigens

The histamine-releasing capability ofStaphylococcus aureus antigens was examined in human adenoidal and mesenteric mast cells obtained by enzymic dispersion of tissues from non-allergic patients. Both populations of mast cells released histamine after challenge with bacterial protein in concentrations between 5–500 g/ml. The release was dependent on the dose, temperature and metabolic energy. The maximum release was observed at 15 min after challenge. The present results suggest thatStaphylococcus aureus antigens release histamine from human adenoidal and mesenteric mast cells via a non-cytotoxic, active secretory process.     

肝素对人肥大细胞组胺分泌的调节作用

目的　研究肝素对人肥大细胞组胺释放的影响。方法　经酶消化后的肺和扁桃体组织的细胞成份同肝素、抗人IgE抗体或钙离子导入剂共同培养 ,以特制的纤维玻璃为基础的方法测量组胺。结果　经 15和 4 5min培养 ,肝素对人肺和扁桃体组织肥大细胞组胺释放无明显影响。而将肝素与抗IgE抗体同时加入酶悬浮的肺肥大细胞中 (预培养时间为 0min) ,肝素可抑制 5 0 %的抗IgE抗体诱导的组胺释放 ,且抑制率与肝素浓度呈正相关。肝素对抗IgE抗体引起的扁桃体肥大细胞的组胺释放无抑制作用 ,对钙离子导入剂诱导的肺和扁桃体的肥大细胞组胺释放无明显影响。结论　本实验首次发现肝素可以抑制抗IgE抗体诱导的人肺肥大细胞组胺释放 ,因此在肺部的变态反应性炎症中可能起到一定的预防和治疗作用     

The modulatory effects of WE-14 on histamine release from rat peritoneal mast cells

Inflammation Research -     

Non-IgE-dependent bacteria-induced histamine release from human lung and tonsillar mast cells

A wide spectrum of formalin-killed bacteria have been tested for their ability to release histamine from human dispersed lung and tonsillar mast cells. Escherichia coli, Enterobacter cloacae, Staphylococcus epidermidis, Proteus vulgaris, Klebsiella oxytoca and K. pneumoniae were the most effective histamine releasers. Further studies on tonsillar masl cells showed that E. coli -induced histamine release differed from IgE-dependent release with respect to its kinetics, temperature and pH profiles and its sensitivity to calcium deprivation and metabolic inhibitors. A lectin-mediated mechanism may operate, but other non-immunological mechanisms might also be involved in the release. Escherichia coli and anti-IgE did not synergize in inducing histamine release. The production of PGD₂ and the failure to detect lactate dehydrogenase following incubation of mast cells with E. coli suggests that histamine release is not due to cytotoxicity.     

类胰蛋白酶抑制剂对人大肠肥大细胞组胺释放的影响

目的 :研究类胰蛋白酶抑制剂 (TPI)对人大肠肥大细胞释放组胺的影响。方法 :大肠组织经胶原酶和透明质酸酶消化后 ,将细胞成分用全HBSS重新悬浮。肥大细胞在LP4试管中于37℃条件下与各种刺激剂反应 15min而完成激发过程。激发液中的组胺水平用以玻璃纤维为基础的荧光方法测定。结果 :4种TPI中 ,高浓度的亮抑酶肽素和鱼精蛋白可刺激人大肠肥大细胞释放组胺 ;而TLCK和乳铁蛋白则无明显的刺激作用。 4种TPI均可以剂量依赖的方式抑制抗IgE抗体诱导的大肠肥大细胞释放组胺。最大浓度的亮抑酶肽素(2 0 0mmol/L)、TLCK(10 0mmol/L)、乳铁蛋白 (30mmol/L)和鱼精蛋白 (10 0mg/L) ,可分别抑制 4 8.7%、36 .7%、4 0 .2 %和 34.1%的组胺释放。在 37℃条件下 ,将 4种TPI同大肠肥大细胞预培养 2 0min ,与未进行预培养相比较 ,它们对抗IgE抗体诱导的组胺释放无明显改变。 4种TPI还可抑制CI诱导的组胺释放 ,抑制范围在 2 5 %～ 32 %之间。与抗IgE抗体诱导的组胺释放则不同 ,与大肠肥大细胞预培养 2 0min ,与未进行预培养相比较 ,亮抑酶肽素和TLCK对CI诱导的组胺释放的抑制作用明显增强 ;而鱼精蛋白则无此作用。结论 :我们首次发现TPI可抑制人大肠肥大细胞IgE抗体依赖和非IgE抗体依赖的组胺释放 ,提示TPI可望成为炎症性肠     

Forskolin inhibits the release of histamine from human basophils and mast cells

We found that forskolin (10^–7 to 3×10^–5 M) caused dose-related inhibition of antigen-induced histamine release from human basophil leukocytes. The dose-response inhibition curve was paralleled by a forskolin-induced increase in cyclic AMP (cAMP) levels in human leukocyte preparations. The kinetics of inhibition of histamine release and of the increase in leukocyte cAMP were the same.In a second series of experiments we evaluated the effect of forskolin on antigen-induced histamine release from chopped human lung passively sensitized with serum from an allergic patient. Forskolin (10^–7 to 3×10^–5 M) dosedependently inhibited the release of histamine from human lung mast cells. Thus forskolin appears to modulate the release of mediators of the immediate hypersensitivity reaction, presumably through activation of adenylate cyclase in human basophils and mast cells.Supported by Grants from the C.N.R. (83.00430.04 and 84.01756.04) and M.P.I. (Rome, Italy).