Effects of tannins and related polyphenols on superoxide-induced histamine release from rat peritoneal mast cells.

The effects of tannins and related polyphenols on KO2- and compound 48/80-induced histamine release from rat peritoneal mast cells were examined. Pretreatment with hydrolyzable tannins (1-100 microM) significantly inhibited KO2-induced histamine release. Dimeric ellagitannins, which have hexahydroxydiphenoyl (HHDP) and valoneoyl residues and/or a valoneoyl-related acyl unit in the molecule, showed more potent inhibitory effects than monomeric hydrolyzable tannins. The most effective inhibition was exhibited by agrimoniin and euphorbin C (IC50 0.68 and 0.80 microM), which have dehydrodigalloyl and euphorbinoyl groups, respectively, as well as the HHDP group. However, procyanidins, flavonoids and related polyphenols with small molecular weights, except for epigallocatechin gallate, exhibited negligible effects. Although clinically used antiallergic drugs, azelastine, astemizole, ketotifen and epinastine have been shown to prevent KO2-induced histamine release, their potencies were all less than those of ellagitannins. An inhibitory effect on compound 48/80-induced histamine release was also exhibited by higher molecular weight tannins. The inhibitory effect on histamine release caused by different stimulants suggested that ellagitannins act as cell membrane stabilizers as well as radical scavengers.     

Rapid inhibitory effect of corticosterone on histamine release from rat peritoneal mast cells.

Glucocorticoids are steroids endowed with powerful anti-inflammatory properties, which are routinely believed to require several hours to take effect through modulation of gene expression. Our recent report has shown that glucocorticoids could inhibit allergic reaction within 10 minutes, which the classical genomic mechanism could not explain. Histamine is thought to be one of major mediators in the allergic reaction, and IgE-mediated histamine release from mast cells plays a pivotal role in allergic diseases. Here, we have determined a rapid effect of corticosterone on histamine release from rat peritoneal mast cells, using fluorometric assay. The results showed that corticosterone could inhibit antigen-induced histamine release from rat peritoneal cells within 15 minutes (p<0.05), which could be mimicked by membrane-impermeable BSA conjugated corticosterone (p<0.05). Neither glucocorticoid nuclear receptor antagonist nor protein synthesis inhibitor could block the rapid action (p<0.05). The study provided evidence that nongenomic mechanism might be involved in rapid effect of glucocorticoids on mast cells in allergic disease.     

Effect of polyethyleneglycol (PEG) on spontaneous and polymyxin B-induced histamine release from rat peritoneal mast cells

Mast cells were isolated from the peritoneal cavity of rat and purified by centrifugation in a gradient of Percoll. The spontaneous and polymyxin B-induced release of histamine was studied after preincubation of the cells with polyethyleneglycols (PEGs) of different molecular weight (200-20,000 dalton) and with fatty acid derivatives of PEG 6000. It was found that very low concentrations (less than 0.1%) of PEG 6000 reduced the spontaneous and polymyxin B-induced release of histamine to a greater extent than the same concentration of bovine serum albumin. The inhibition increased with the size of the PEGs, but was little affected by the presence of fatty acid ligand bound to PEG.     

Effect of calcium on histamine release from pleural and peritoneal mast cells induced by catechol

Histamine release from rat pleural and peritoneal mast cells induced by catechol (1, 10, 50, 250 microM and 1 mM) has been studied. The dose-response induced by catechol is non-cytotoxic, is not modified by purification of mast cells and is calcium independent. The sensitivity and maximum response to catechol is the same irrespective of the presence or absence of Ca++, except on purified pleural mast cells, that showed a plateau response at 250 microM catechol in the absence of Ca++, and on unpurified peritoneal mast cells which exhibited a lower maximum response equally in the absence of Ca++. The release is induced by catechol at concentrations as low as 50 microM in all cases, and the maximum response is reached at 1 mM.     

Strain differences in histamine release from mouse peritoneal mast cells induced by compound 48/80 or A23187

Strain differences among BALB/c, BDF1, CDF1, C3 H/He, C57 BL/6, DBA/2, ddy and ICR mice were investigated with respect to the ratios of histamine release from mouse peritoneal mast cells induced by compound 48/80, a Ca2+ dependent histamine releaser, and the Ca2+ ionophore A23187. The ratios of histamine release from mouse peritoneal mast cells induced by compound 48/80 were found to be high in BALB/c, ddY and ICR mice, but low in BDF1, CDF1, C3 H/He, C57 BL/6 and DBA/2 mice. Those induced by Ca2+ ionophore A23187 were high in BALB/c, BDF1, CDF1, C3 H/He, DBA2, ddy and ICR mice but low in C57 BL/6 mice. These results indicate that differences in histamine release from mouse peritoneal mast cells are strain dependent.     

Biochemical analysis of glucocorticoid-induced inhibition of IgE-mediated histamine release from mouse mast cells

Pretreatment of mouse mast cells with 10(-7) to 10(-6) M dexamethasone (DM) during overnight sensitization with mouse IgE antibody resulted in inhibition of antigen-induced histamine release and degranulation. The inhibition of both degranulation and histamine release increased linearly with the duration of the treatment; maximal inhibition was obtained after approximately 16 hr with DM. The addition of DM to sensitized mast cells immediately before antigen challenge did not affect the antigen-induced histamine release. DM interacted directly with mast cells by binding to DM-specific cytoplasmic receptors. The treatment of mast cells with DM did not affect the binding of IgE to mast cells or intracellular cAMP levels. Bridging of cell-bound IgE anti-DNP antibody on mouse mast cells either by multivalent DNP-HSA or by anti-IgE induced phospholipid methylation at the plasma membrane and Ca++ influx into the cells. Pretreatment of mast cells with DM inhibited the antigen-induced phospholipid methylation and Ca++ uptake but failed to affect histamine release by Ca++ ionophore A23187. The results suggest that DM treatment inhibits histamine release by the inhibition of the early stage of biochemical processes leading to opening Ca++ channels but does not affect the process distal to Ca++ influx or the binding of IgE molecules to IgE receptors.     

Low density lipoprotein (LDL) inhibits histamine release from human mast cells

We examined the effect of low density lipoprotein (LDL) on histamine release from purified human lung mast cells. LDL inhibited anti-IgE- induced histamine release in a dose-dependent manner, with 100 micrograms/ml LDL-protein inhibiting histamine release by 53 +/- 8% (mean +/- SEM); half-maximal inhibition occurred at 40-80 micrograms/ml. LDL also inhibited calcium ionophore A23187-induced histamine release in a dose-dependent manner, with 1 mg/ml of LDL inhibiting histamine release by 83 +/- 9%; half maximal inhibition occurred at 220-280 micrograms/ml. Inhibition by LDL was time-dependent: half-maximal inhibition of anti-IgE- induced histamine release by LDL occurred at 30-50 minutes of incubation. The inhibitory effect of LDL was independent of buffer calcium concentrations (0-5 mM) or temperature (0-37 degrees C). These data are consistent with a newly defined immunoregulatory role for LDL.     

The effect of calmodulin on histamine release in the rat peritoneal mast cell

To investigate the role of the Ca²⁺-binding protein calmodulin on histamine release in the rat peritoneal mast cell, we exposed cells to exogenous calmodulin in the presence of a variety of histamine secretagogues. Histamine release stimulated by compound , polymyxin B and ionophore A23187 was inhibited while concanavalin A-stimulated release was not affected. Calmodulin in the presence of the secretagogues did not affect cell viability and calmodulin alone had no effect on histamine release. No direct interaction between calmodulin and the secretagogues was observed. Exogenous calmodulin does not appear to be incorporated into the cell. The inhibition of histamine release by calmodulin can be explained as a labile interaction between the protein and the cell that requires externally-bound Ca²⁺. These experiments demonstrate the use of exogenous calmodulin as a probe in the study of the mechanism of histamine release.     

The effect of calmodulin on histamine release in the rat peritoneal mast cell

To investigate the role of the Ca2+-binding protein calmodulin on histamine release in the rat peritoneal mast cell, we exposed cells to exogenous calmodulin in the presence of a variety of histamine secretagogues. Histamine release stimulated by compound 48/80, polymyxin B and ionophore A23187 was inhibited while concanavalin A-stimulated release was not affected. Calmodulin in the presence of the secretagogues did not affect cell viability and calmodulin alone had no effect on histamine release. No direct interaction between calmodulin and the secretagogues was observed. Exogenous calmodulin does not appear to be incorporated into the cell. The inhibition of histamine release by calmodulin can be explained as a labile interaction between the protein and the cell that requires externally-bound Ca2+. These experiments demonstrate the use of exogenous calmodulin as a probe in the study of the mechanism of histamine release.     

Comparative functional characterization of mouse bone marrow-derived mast cells and peritoneal mast cells in response to non-immunological stimuli

The cultured mouse mast cells that are dependent on spleen-derived factor for their proliferation and maintenance and have been shown to be similar to mucosal mast cells in terms of their T-cell dependence and histochemical staining characteristics. Mast cell heterogeneity has been confirmed by functional characterization of mouse bone marrow-derived mast cells (MBMMC) and mouse peritoneal mast cells (MPMCs). MPMCs released around 30% of histamine when stimulated with compound 48/80 whereas MBMMC were almost unresponsive to the same stimulus. Calcium Ionophore A23187 on the other hand, released histamine in dose-dependent manner from MBMMC. The study was undertaken to investigate the effect of antiallergic drug, disodium cromoglycate (DSCG), a synthetic cromone and quercetin, a plant-derived flavonoid on Ca ionophore A23187 induced histamine release from MBMMC. MBMMCs were almost unresponsive to DSCG whereas Ca Ionophore induced histamine release was blocked by Quercetin. The results indicate that response of mast cells at one anatomic site to a given stimulus does not necessarily predict the response of mast cells at a different anatomic location to the same stimulus. It shows functional heterogeneity within a single species. So, it cannot be assumed that antiallergic compounds stabilizing mast cells in one tissue site or organ will be equally efficacious against mast cells in other sites.     

Comparison of circulating and peritoneal leukocyte cationic proteins in release of histamine from rat mast cells

Lysosomal cationic proteins which release histamine from rat peritoneal mast cells were prepared from circulating as well as peritoneal leukocytes of rabbits. The release of histamine by cationic proteins and by compound $\text{48}\text{80}$ was compared as a function of temperature, pH and concentration. Cationic protein-mediated histamine release appears to be a non-cytotoxic energy requiring process similar to compound $\text{48}\text{80}\text{-}\text{mediated release}$. It was inhibited by iodoacetate, n-ethylmaleimide, 2,4-dinitrophenol, malonate, oxamate, glutamate and slightly inhibited by 2-deoxyglucose. Pharmacologic inhibition of release by isoproterenol, aminophylline, dibutyryl cyclic AMP and prednisone was also demonstrated.     

Effect of NCDC, a protease inhibitor, on histamine release from rat peritoneal mast cells induced by anti-IgE.

NCDC dose-dependently inhibited histamine release from rat peritoneal mast cells induced by anti-IgE. Moreover, NCDC inhibited Ca(2+)-mobilization from intracellular Ca(2+)-stores as well as histamine release in mast cells activated by anti IgE, the effect on both of these phenomena being closely correlated. Anti-IgE induced a rapid increase in IP3 production from phosphoinositides in mast cells, with its production in 15 sec, followed to baseline levels within 1 min. Anti-IgE stimulated PLC activity on mast cells membrane preparation. NCDC dose-dependently inhibited the generation of IP3. These results suggest that the inhibitory effect of NCDC on the release of histamine induced by anti-IgE is due to, in part at least, the inhibition of PI-specific PLC and that the inhibitory effects of NCDC are involved in intracellular calcium store.     

Differential calcium effects on prostaglandin D2 generation and histamine release from isolated rat peritoneal mast cells

We examined the role of Ca2+ mobilization in prostaglandin (PG) D2 generation and histamine release induced by A23187 from rat peritoneal mast cells. Both PGD2 generation and histamine release accompanied with 45Ca uptake were observed above 0.1 microM A23187. Although an increase of PGD2 generation was not exactly correlated with that of Ca2+ uptake, histamine release occurred in proportion to Ca2+ uptake. In contrast to PGD2 generation, below 0.1 microM A23187, about 20% of the total histamine was released without Ca2+ uptake and this response was inhibited by 10 microM 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), which is an intracellular Ca2+ antagonist. However, TMB-8 had no effect on PGD2 generation. These results suggest that Ca2+ dependency of histamine release is clearly different from that of PGD2 generation, and that histamine release is induced by not only Ca2+ uptake but also intracellular Ca2+ mobilization.     

Dual effects of protoporphyrin and long wave ultraviolet light on histamine release from rat peritoneal and cutaneous mast cells.

In this study we investigated the effects of long wave ultraviolet light (UVA) and various doses of protoporphyrin (PP) on the release of histamine from rat peritoneal and cutaneous mast cells. We also correlated these results with morphologic characteristics and viability of the cells. PP at a dose of 30 ng/ml plus UVA-induced negligible histamine release from rat peritoneal mast cells (RPMC), but was able to suppress the ability of the cells to release histamine in response to subsequent exposure to the calcium ionophore A23187, compound 48/80, or the combination of Ag and IgE. This functional change was associated with an increase in cell size, and cell lysis that gradually occurred during 24 h in culture. PP at a dose of 3 ng/ml plus UVA also significantly inhibited secretogogue-induced histamine release from rat peritoneal mast cells, but this dose was not associated with significant changes in morphology or viability. These various effects of PP plus UVA were also observed with mast cell preparations obtained by the enzymatic dispersion of rat skin. The suppression of secretogogue-induced histamine release in rat peritoneal mast cells treated with PP (3 ng/ml) and UVA could not be reversed by culturing the cells in the dark for 24 h in the absence of PP. Unlike the direct cytotoxic histamine releasing action of high doses of PP plus UVA, the suppressive effect of low PP doses could not be inhibited by catalase, but could be reduced by the absence of calcium. Our results indicate that PP plus UVA has dual effects on mast cells, apparently involving distinct mechanisms. This implies the possibility that PP and UVA at appropriate doses could be used in photochemotherapy of mast cell-mediated skin diseases.