Some studies on the release of histamine from mast cells stimulated with polylysine.

1 Polylysine is an extremely potent releaser of histamine from rat peritoneal mast cells. Isolated mesenteric mast cells of the rat also respond to the secretagogue but guinea-pig mesenteric cells are unreactive. 2 The release does not require the presence of extracellular calcium ions but shows some dependence on internal stores of the cation. 3 The effect of polylysine is blocked by extremes of temperature and by metabolic inhibitors. 4 The release is very rapid and is virtually complete within 10 s of adding the inducer. 5 The release is unaffected by the anti-allergic drug, doxantrazole, but is inhibited by theophylline and disodium cromoglycate. The latter compounds are effective in both the presence and absence of added calcium. This result is discussed in terms of the postulated effect of the drugs on calcium transport.     

Anthracycline-induced histamine release from rat mast cells

Comparisons were made of the ability of doxorubicin, daunorubicin, rubidazone and aclacinomycin A to release histamine from rat peritoneal mast cells. Preliminary in vitro experiments indicated that doxorubicin (10(-6) to 2.5 X 10(-4) M), in contrast to compound 48/80 and the calcium ionophore A23187, did not produce significant release under any condition tested when purified or unpurified rat mast cells were used. In in vitro experiments, released histamine was measured in the cell-free supernatant of peritoneal fluid of rats after intraperitoneal injection of the agents. The time course of doxorubicin-induced histamine release from the peritoneum was rapid, with maximal release occurring within 4 to 6 min. Dose-response curves of the 4 agents over the range 10(-5) to 3.3 X 10(-3) M revealed that all caused histamine release, with 10(-3) M concentrations of each causing maximal release of comparable magnitude to that produced by 9.5 X 10(-6) M A23187. Treated mast cells recovered from the peritoneal cavity showed degranulation and vacuolization when examined by electron microscopy. Increased vascular permeability by the Evans-blue test was also noted with all 4 agents, and zones were of comparable size after injection of the highest concentration of each agent. The results indicate that in vivo, doxorubicin, daunorubicin, rubidazone and aclacinomycin A cause a rapid release of histamine from rat mast cells and an increase in vascular permeability in rat sin. There also appeared to be a reasonable correlation between the blueing reaction and histamine release in the peritoneal cavity in that the doses that did not cause skin blueing also failed to cause histamine release. The lack of histamine release by doxorubicin from mast cell preparations in vitro suggests that alterations to the doxorubicin molecule or the presence of other critical substances may be necessary for this activity to commence.     

Effect of methylmercury on histamine release from rat mast cells

Methylmercury chloride (MeHgCl) is well known as a significant environmental hazard, particularly as a modulator of the immune system. As it is acknowledged that the critical effector cells in the host response participating in various biological responses are mast cells, we tried to define the possible contribution of mast cells in the development of methylmercury-evoked effects. We investigated the effects of methylmercury on the rat mast cell degranulation induced by non-immunological stimuli (the selective liberator of histamine, compound 48/80, and calcium ionophore A23187) both in vivo and in vitro. Using the cells prepared from methylmercury-intoxicated rats through a 5-day treatment of MeHgCl (10 mg/kg/day), we observed the suppression of calcium ionophore A23187- and 48/80-induced histamine release, which was enhanced with time after treatment. Similar suppression was observed in the ionophore-stimulated release, when cells were prepared from rat with a single treatment of MeHgCl (20 mg/kg). It should be noted that when cells from the control rat were pre-incubated with methylmercury in vitro at a 10(-8) M concentration for 10 min, A23187 and compound 48/80-stimulated histamine release was significantly enhanced. However, when the pre-incubation period was prolonged to 30 min, the release was suppressed. An increase in the methylmercury concentration to 10(-6) M also suppressed the histamine release. These results show that methylmercury treatment can modify mast cell function depending on concentration and time, and might provide an insight into the role of mast cells in the development of methylmercury-stimulated effects.     

FMLP-activated neutrophils evoke histamine release from mast cells

Human neutrophils, having been activated by the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP), evoke histamine release from rat serosal mast cells. The release is dependent on FMLP concentration and it can be inhibited by disodium cromoglycate and by a flavonoid, silymarin, which displays free radical scavenging properties. Silymarin inhibition of neutrophil-mediated histamine release is dose-dependent. These results further stress the concept of a neutrophil-mast cell interaction, which may be involved in inflammatory processes.     

Inhibitory mechanism of tritoqualine on histamine release from mast cells

Tritoqualine (TRQ, (+)-(R*)-7-amino-4,5,6-triethoxy-3-[(R*)-5,6,7, 8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin++ +-5-yl] phthalide) strongly inhibited the increased metabolism of [3H]arachidonic acid-labeled phospholipid and 45Ca2+ influx in mast cells stimulated by compound 48/80 (compd 48/80), Concanavalin A (Con A) plus phosphatidylserine (PS), or 2,4-dinitrophenyl-coupled-ascaris extracts (DNP-asc). However, TRQ did not disturb the binding of 14C-labeled compd 48/80 to the mast cell membrane. The activity of calmodulin purified from mastocytoma P-815 cells was inhibited by TRQ at IC50 1.0 microM. From these results, it is concluded that the inhibitory mechanism of TRQ on stimulus-induced histamine release from mast cells may be mediated at least partially by the inhibition of Ca2+ influx and calmodulin activity.     

Effect of triphenyltin chloride on the release of histamine from mast cells

The effects of triphenyltin chloride (TPTC) on the release of histamine from rat and mouse mast cells in vitro and in vivo were investigated. The results obtained are summarized as follows: (a) At doses between 1 and 3 mg/kg, TPTC inhibited the dye leakage due to passive cutaneous anaphylaxis mediated by IgE antibody in mouse ear. At the same doses, TPTC inhibited the swelling due to reversed cutaneous anaphylaxis mediated by IgG antibody in rat. However, TPTC did not affect dye leakage due to histamine, serotonin, and LTC₄ in rat skin; (b) Histamine release by antigen and IgE antibody in rat peritoneal cavity was inhibited by the administration of TPTC at doses between 0.3 and 3 mg/kg; (c) Histamine release by calcium ionophore A 23187 from purified rat peritoneal mast cells in vitro was inhibited by TPTC at concentrations between 10^–7 and 10^–6 M. At the same concentration, TPTC, itself, caused neither the release of histamine nor any change in cell viability which was supported by the activity of lactate dehydrogenase (LDH) from purified rat peritoneal mast cells. All this evidence suggests that TPTC has an inhibitory effect on the release of histamine from mast cells without direct cytotoxicity.     

Effect of calcium on dextran-induced histamine release from isolated mast cells

Phosphatidyl serine potentiation of dextran-induced histamine release from isolated rat mast cells, was found to be calcium-dependent.     

Dependence of histamine release from rat mast cells on adenosine triphosphate

Summary using pure populations of rat mast cells, the relation of the ATP content of the cells to histamine release induced by compound 48/80 has been studied. Variable ATP levels in the mast cells have been produced by incubation with appropriate concentrations of oligomycin.The dose-response curves of oligomycin for the inhibition of histamine release and for the reduction in the ATP content of the mast cells are similar. The concentration required for 50% inhibition of histamine release is, however, higher than that for 50% reduction of the ATP level.Comparative study of the reduction of the ATP content and the inhibition of histamine release in samples of the same suspension of mast cells shows a linear relation between 10 to 90% inhibition of histamine release and 40 to 95% inhibition of ATP synthesis.The observations support the hypothesis that ATP is involved in the process of histamine release from mast cells induced by compound 48/80.     

Peptides and histamine release from rat peritoneal mast cells

Various vasoactive peptides were compared for their histamine releasing effects on rat mast cells. Neurotensin, substance P (SP), and kallidin were the most active natural peptides, followed by bradykinin; neurokinin A and B, bombesin, angiotensin and tuftsin were practically inactive. Several kinins and tachykinin-related peptides were tested in an attempt to characterize the receptors mediating histamine liberation. The order of potency of the kinins was the following: kallidin greater than [Tyr(Me)8]bradykinin = bradykinin greater than [desArg10]kallidin greater than desArg9-bradykinin, the same as that found in smooth muscle possessing receptors of the B2 type. Tachykinin-related peptides were potent stimulants and followed the order: [D-Tryp7,9,10]SP-(1-11) greater than [D-Pro2,D-Tryp7,9,10]SP-(1-11) greater than SP-(1-11) greater than SP-(1-9) greater than [D-Pro4,D-Tryp7,9,Leu11]SP-(4-11) greater than SP-(1-7) greater than SP-(4-11) greater than neurokinin A = neurokinin B, indicating that: (a) undecapeptide antagonists of SP behave as superagonists; (b) both N- and C-terminal portions of SP-(1-11) are essential for activity; and (c) receptors for the tachykinins mediating histamine release appear to be of the SP-P type.     

Properties of hydrogen peroxide-induced histamine release from rat mast cells

Incubation of rat peritoneal mast cells with hydrogen peroxide results in a marked release of histamine. Maximal release is observed with 0.05–0.1 mM H₂O₂, but higher concentrations of H₂O₂ instead suppresses the release. Histamine release starts after about 2 min of lag time and reaches a plateau in about 10 min. Hydrogen peroxide-induced release does not exceed 50–60 per cent of total histamine if the incubations are prolonged or additional H₂O₂ is given at 10 min. This would be explained by the fact that H₂O₂ causes impairment of the histamine releasing system of mast cells simultaneously with the release of histamine. Hydrogen peroxide-induced release is not due to nonspecific lysis of the cells because lactate dehydrogenase, a cytoplasmic enzyme, is not liberated during the reaction. The reaction requires the presence of Ca²⁺, is enhanced by D₂O and suppressed by colchicine. It is not, however, affected by dibutyryl cAMP or dibutyryl cGMP. No significant alteration of intracellular levels of cyclic AMP and cyclic GMP is observed during the incubation of mast cells with 0.1 mM H₂O₂. These results indicate that microtubular functions would be involved in the releasing reaction although they are not under the control of cyclic nucleotides. Microscopic observation shows that H₂O₂-induced release is accompanied by degranulation.     

Lectin-induced histamine release from various populations of hamster mast cells

Peritoneal, pleural and cheek pouch mast cells from Syrian hamsters were tested for their reactivity to the action of concanavalin A and the lectin from Canavalia brasiliensis. Both lectins induced dose-dependent histamine release from hamster mast cells but the magnitude of release was different in the three mast cell populations (peritoneal greater than pleural greater than cheek pouch mast cells). The lectin from Canavalia brasiliensis was a more potent histamine releaser than concanavalin A for the peritoneal and pleural mast cells. The responsiveness of these two populations of mast cells to the action of both lectins was dependent on the age of hamsters; in young animals up to six months old it increased with their age, whereas in older animals a slight decrease of the responsiveness was observed. Our results support the view that mast cells from different locations and from animals of different ages may show marked variations in their histamine releasing properties.     

Inhibitory effect of lysophosphatidylcholine on the histamine release from rat peritoneal mast cells

Histamine release from isolated rat peritoneal mast cells induced by compound 48/80 (0.5 microgram/ml) or antigen-antibody reaction was inhibited by lysophosphatidylcholine in a dose-dependent fashion at concentrations up to 4 microM. Within the same range of concentration, lysophosphatidylcholine exhibited a membrane-stabilizing action on the model membrane systems decreasing the permeability of lipid bilayer and the fluidity of liposomal membrane in the liquid crystalline state. At concentrations higher than 8 microM, lysophosphatidylcholine damaged the cell membrane and subsequently histamine was released. It was assumed that lysophosphatidylcholine may act as an endogenous membrane stabilizer inhibiting histamine release in normal mast cells.     

Salmeterol inhibits anaphylactic histamine release from guinea-pig isolated mast cells

Abstract— Salmeterol (1 Nm-100μm) showed an inhibitory action on anaphylactic histamine release from mast cells, isolated from pleural and peritoneal cavities of actively sensitized guinea-pigs and stimulated by incubation with allergen. The effect is concentration-dependent and is reduced by the β-adrenoceptor antagonist propranolol (1 μm). This study supports the hypothesis of an antiinflammatory property of salmeterol, which concerns cells involved in the early phases of asthma.     

类糜蛋白酶抑制剂对人结肠肥大细胞组胺释放的影响

目的　研究类糜蛋白酶抑制剂对人结肠肥大细胞释放组胺的影响。方法　用酶消化人结肠组织并分离细胞成份。激发过程在LP4试管中、37℃条件下完成。组胺水平用以玻璃纤维为基础的荧光方法测定。结果　类糜蛋白酶抑制剂ZIGPFM、TPCK和α1 抗胰蛋白酶无明显刺激人类结肠肥大细胞释放组胺的作用。 3种类糜蛋白酶抑制剂均可以剂量依赖性方式抑制抗IgE抗体诱导的组胺释放 ,最大浓度的ZIGPFM(1mmol·L-1)、TPCK(80mmol·L-1)和α1 抗胰蛋白酶(30mmol·L-1)可分别抑制 37%、2 6 %和 36 8%的组胺释放。在 37℃条件下同结肠细胞预培养 2 0min与无预培养相比 ,ZIGPFM和TPCK抑制抗IgE抗体诱导的组胺释放的作用略有增强。 3种类糜蛋白酶抑制剂均可以剂量依赖性方式抑制CI诱导的组胺释放 ,最大抑制范围在 2 3 6 %～ 35 %之间。在 37℃条件下同结肠细胞预培养 2 0min与无预培养相比 ,TPCK对CI诱导的组胺释放的抑制作用略有增强 ,但ZIGPFM则无此特点。结论　我们发现了类糜蛋白酶抑制剂可抑制人结肠肥大细胞IgE依赖性和非依赖性组胺释放 ,提示类糜蛋白酶抑制剂可能有抗炎症性肠病的作用 ,可研究开发     

Effect of cromoglycate on anaphylactic histamine release from rat peritoneal mast cells

Cromoglycate (1-30 muM) produced a concentration-dependent inhibition of anaphylactic histamine release from actively sensitized rat peritoneal mast cells but at lower concentrations (0.01-0.1 muM) occasionally produced a concentration-dependent enhancement of histamine release.     

Prostaglandin and histamine release from stimulated rat peritoneal mast cells

The production of five prostanoids (PGD2, PGE2, PGF2 alpha, 6-oxo-PGF1 alpha, and TxB2) was examined after mast cell activation. Prostaglandin D2 (PGD2) was the major prostanoid produced after stimulation of rat peritoneal mast cells with the calcium ionophore A 23187, compound 48/80 or anti-rat IgE. The amount of PGD2 generated was not dependent on the quantity of histamine released. The time course of PGD2 production paralleled the release of histamine following activation with A 23187 or anti-rat IgE but with compound 48/80 release of histamine reached a maximum within 15 sec, whereas production of PGD2 was apparent only after 5 min and was still increasing at 30 min.     

Inhibitory effect of phloretin on histamine release from isolated rat mast cells

The ability of the flavonoid phloretin to inhibit histamine release from rat mast cells varied considerably with the releasing agent investigated. The response to the combination of the ionophore A23187 and the phorbol ester TPA and to suboptimal concentrations of the ionophore (0.5 microM) was potently inhibited (IC50 about 5 microM), whereas phloretin was less potent against responses to the ionophore (1 microM) (IC50 of 17 microM), to antigen alone and in combination with TPA (IC50 of 30-50 microM), to TPA in the absence of calcium (IC50 of 50 microM) and to compound 48/80 in the absence and presence of calcium (IC50 of 60-90 microM). The inhibition by phloretin at concentrations above 10 microM was partly counteracted by glucose (5 mM) indicating effects on oxidative metabolism. The flavonoid quercetin was equally potent in inhibiting histamine release induced by antigen, the ionophore at different concentrations and in combination with TPA (IC50 of 20 microM). Although not conclusive, the results are consistent with an inhibition of protein kinase C by phloretin at concentrations below 10 microM. At higher concentrations unspecific actions become apparent and phloretin therefore seems to be of limited utility as a probe for signal-pathways in cell responses.