Mitochondrial signaling for histamine releases in laser-irradiated RBL-2H3 mast cells.

BACKGROUND: The low power laser irradiation (LPLI) can promote the wound healing, but the mechanism is still not fully understood. We have found in our previous work that the LPLI induces mast cells to release the histamine and thus suggested that the increased histamine release is probably one of the causes for promoting the wound healing since mast cells have been found to play positive roles in the process of wound healing. This study aims to explore the mechanism of histamine release in RBL-2H3 mast cells under laser irradiations. MATERIALS AND METHODS: The wavelength effect of laser irradiations, the permeability function of mitochondrial membrane, the Bcl-2 effect, the cytosolic alkalinization and the increment of intracellular Ca(2+) ([Ca(2+)](i)), on histamine release in RBL-2H3 cells were studied, respectively, with the corresponding fluorescence probes. RESULTS: The action bands of laser irradiations were consistent with the absorption bands of cytochrome c oxidase, suggesting that cytochrome c oxidase is the photoacceptor. After laser irradiation, (1) the cytochrome c releases from mitochondrial to cytosol reflecting an increased permeability of mitochondrial membrane, (2) the cytosolic alkalinization appears, (3) [Ca(2+)](i) increases, and (4) finally the enhancement of histamine release occurs. When Bcl-2 was used to inhibit the permeability of mitochondrial membrane these cellular signaling from (1) to (4) were all suppressed obviously. CONCLUSION: As a photoacceptor, cytochrome c oxidase absorbs incident photons and initiates the mitochondrial signaling. When the signals are transferred from the mitochondrial to the cytosol, the cytosolic alkalinization appears leading to the opening of a Ca(2+) channel on the membrane, the transient receptor potential vanilloid (TRPV), and an increment of [Ca(2+)](i). The increased [Ca(2+)](i) consequently mediates an enhanced histamine release. Such a responding chain is a suggested mechanism to understand the histamine release in RBL-2H3 cells under laser irradiations.

Effects of low power laser irradiation on intracellular calcium and histamine release in RBL-2H3 mast cells.

Although laser irradiation has been reported to promote skin wound healing, the mechanism is still unclear. As mast cells are found to accumulate at the site of skin wounds we hypothesized that mast cells might be involved in the biological effects of laser irradiation. In this work the mast cells, RBL-2H3, were used in vitro to investigate the effects of laser irradiation on cellular responses. After laser irradiation, the amount of intracellular calcium ([Ca2+]i) was increased, followed by histamine release, as measured by confocal fluorescence microscopy with Fluo-3/AM staining and a fluorescence spectrometer with o-phthalaldehyde staining, respectively. The histamine release was mediated by the increment of [Ca2+]i from the influx of the extracellular buffer solution through the cation channel protein, transient receptor potential vanilloid 4 (TRPV4). The TRPV4 inhibitor, Ruthenium Red (RR) can effectively block such histamine release, indicating that TRPV4 was the key factor responding to laser irradiation. These induced responses of mast cells may provide an explanation for the biological effects of laser irradiation on promoting wound healing, as histamine is known to have multi-functions on accelerating wound healing.

Involvement of histamine released from mast cells in acute radiation dermatitis in mice.

A possible involvement of histamine in acute radiation dermatitis in mice was investigated. The dose of 40 Gy of gamma irradiation induced erythema and edema in C57BL/6 mice treated with vehicle. However, in C57BL/6 mice treated with chlorpheniramine and WBB6F1-W/Wv mice, erythema and edema were not observed. In all of these mice, epilation and dry desquamation were induced, but bepotastine significantly reduced the extent of these areas. These results suggest that gamma irradiation-induced erythema and edema were caused by histamine released from mast cells via histamine H1 receptor, and epilation was induced by other inflammatory mediators.

Bivalent effect of UV light on human skin mast cells-low-level mediator release at baseline but potent suppression upon mast cell triggering.

Ultraviolet (UV) irradiation is an established treatment for inflammatory skin diseases, although the precise mode of action is still unclear. Activating and suppressive effects on mast cell (MC) mediator release have been described. The aim of this study was to investigate systematically the effects of UVB, UVA-1, and psoralen plus UVA-1 at therapeutic doses on skin-derived human MC. Baseline and stimulated release of histamine, tryptase, and of interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were examined. In resting MC, UV light induced a slight, yet significant histamine release corresponding to enhanced surface levels of lysosome-associated membrane proteins (LAMP). In contrast, UV pre-treatment caused a marked suppression of the anti-IgE-induced histamine release, accompanied by a diminished, anti-IgE-mediated increase in LAMP expression. The secretion of IL-6, IL-8, and TNF-alpha was inhibited in resting and activated MC, suggesting a different mode of action. Regarding the importance of MC in a variety of allergic and inflammatory processes, our data show a high susceptibility of this cell type towards UV light, which seems to partially depend on the state of cellular activation. Immunosuppressive effects predominate in activated MC, thus corresponding with the beneficial effects in inflammatory diseases, whereas in resting MC, both stimulatory and inhibitory effects are observed.

Influence of UVB, UVA and UVA1 irradiation on histamine release from human basophils and mast cells in vitro in the presence and absence of antioxidants.

UV irradiation is widely used for the treatment of atopic eczema. In recent years, UVA1 phototherapy has gained increasing attention. This study analyzed the influence of different UV wavelengths--especially UVA1--on histamine release from human basophils and mast cells. The modulation of this parameter might be responsible for some of the therapeutic effects of UV irradiation. Enriched human basophils and human mast cells (HMC1 cell line) were irradiated with increasing doses of UVB, UVA and UVA1 in vitro. After irradiation, different stimulants were added to induce histamine release. In additional experiments, basophils were preincubated with superoxide dismutase, ascorbate or trolox to study the role of antioxidants in the modulation of histamine release after UV irradiation. UVA and UVA1 significantly inhibited histamine release from basophils and mast cells. UVB only had an inhibitory effect on mast cells. Preincubation with superoxide dismutase and ascorbate did not influence the inhibitory effect of UVA1 on basophil histamine release, whereas trolox decreased significantly the histamine release from nonirradiated basophils.

In vitro effects of ultraviolet A on histamine release from human basophils.

BACKGROUND: As long-wave ultraviolet (UV) radiation penetrates the dermis, connective tissue cellular components and circulating blood cells can be possible targets for solar UVA. Basophils, involved in the effector phase of the inflammatory response, play a part in skin diseases such as chronic urticaria, psoriasis, atopic dermatitis, fixed drug eruption, allergic contact dermatitis, urticaria pigmentosa, systemic sclerosis and bullous pemphigoid. OBJECTIVE: The evaluation of the in vitro effect of UVA on histamine release from human basophils. METHODS: Basophils from healthy human volunteers were irradiated, respectively, with UVA at doses of 2.5, 5, 7.5, 10, 20 and 50 J/cm2 and then incubated with an anti-IgE serum. A fluorimetric technique was employed to determine histamine release from samples: (i) incubated with 2% HClO4 (complete lysis of basophils); (ii) irradiated with increasing doses of UVA; and (iii) unirradiated (controls). RESULTS: Histamine release was: 100% for HClO4 incubated basophils, 30% for unirradiated and anti-IgE incubated cells (controls) and 27%, 24%, 34%, 41%, 60% and 70% for basophils irradiated with UVA doses, respectively, of 2.5, 5, 7.5, 10, 20 and 50 J/cm2 and incubated with anti-IgE. Histamine releasability from irradiated samples was statistically significant (P < 0.05), in comparison with controls, at UVA doses equal to 5, 10, 20 and 50 J/cm2. CONCLUSIONS: UVA exerts, at least in vitro, a biphasic dose-dependent action on histamine release from human basophils incubated with an anti-IgE serum: at the lowest irradiation doses (< 5 J/cm2) it exerts an inhibitory effect and at the highest doses (> or = 10 J/cm2) histamine release increases significantly.

Evaluacion de la liberacion de Histamina para el diagnostico de alergia y farmacos mediante un metodo inmunoenzimatico competitivo (ELISA), en poblacion aparentemente sana y poblacion alergica / Evaluation of the liberation of Histamina for I diagnose of allergy to farmacos, by means of metodo inmunoenzimatico competitive (ELISA), in population apparently it heals and alergica population

La alergia a fármacos es un problema importante en salud pública, que día a día tiene mayor. repercusión en nuestra población. Lamentablemente en nuestro medio no se le otorga la debida importancia; por lo que no contamos con fuentes de referencia sobre la incidencia y las consecuencias de esta patología. Esta realidad, también la falta de procedimientos para un diagnostico correcto y de verdadero beneficio para las personas alérgicas, que permitan la identificación de él o los fármacos que potencialmente podrían causar reacciones nocivas y así permitir el uso de medicamentos sin el temor de ocasionar una reacción adversa. En este sentido, pretendimos adecuar una nueva prueba de laboratorio destinada a evaluar la liberación de histamina como una alternativa diagnóstica que sea precisa y que oriente a tomar las acciones más adecuadas en el caso de pacientes con sospecha cíe alergia

Effect of middle-wave ultraviolet irradiation and red light on degranulation of peritoneal mast cell in rats.

Middle-wave UV-irradiation inhibits liberator-induced histamine release from mast cells. Red light stimulated liberator-induced degranulation of mast cell. The existence of a membrane-dependent system activated by long-wave (red) light in mammalian cells is discussed.

Ultraviolet B (UVB) light-induced histamine release from rat peritoneal mast cells and its augmentation by certain phenothiazine compounds.

When rat peritoneal mast cells were exposed to ultraviolet (UV) light (UVA, UVB and UVC), histamine release was evoked in a dose (intensity X time) dependent manner. The potency order of UV light in inducing the histamine release was UVC > UVB >> UVA. In this study, we focused on the effect of ultraviolet B (UVB) on histamine release from rat mast cells. The UVB-induced histamine release occurred at doses higher than 7.8 kJ m(-2), even at 4 degrees C. At a UVB dose of 18.8 kJ m(-2), where a 51.9+/-4.8% histamine release and a 58.8+/-6.8% degranulation took place, Trypan blue-stained cells accounted for 14.4+/-1.3% of the cells, and the lactate dehydrogenase (LDH) release was about 4.9+/-2.8%. This suggests that the membrane permeability to low molecular weight substances was increased by UVB exposure. The UVB-induced histamine release was inhibited by ascorbic acid at concentrations higher than 500 microM, suggesting the involvement of a radical reaction in the process. The UVB-induced histamine release was enhanced by some phenothiazine compounds, i.e., promethazine, trimeprazine, mequitazine, chlorpromazine, trifluoperazine, ethopropazine and thioridazine. We conclude that the phototoxicity of phenothiazine compounds may be due in part to an enhancement of UVB-induced histamine release from mast cells.

Inhibition of substance P-induced histamine release from rat peritoneal mast cells by low doses of protoporphyrin plus long-wave ultraviolet light irradiation: decreased intracellular calcium as a possible mechanism.

BACKGROUND: A considerable amount of recent interest has been devoted to the down-regulatory effects of photosensitizers plus long-wave ultraviolet light (UVA) irradiation on multiple biologic systems. However, these effects on mast cells are controversial. OBJECTIVE: We have investigated the effect of low doses of protoporphyrin (PP) plus UVA irradiation (PP/UVA) on substance P (SP)-induced histamine release from rat mast cells. METHODS: Rat peritoneal mast cells purified on a Percoll gradient were treated with 3 ng/mL PP and/or UVA, and challenged with SP. In some experiments, IgE-sensitized mast cells were stimulated by antirat IgE in the presence of phosphatidylserine. Histamine released from mast cells and intracellular calcium concentrations ([Ca2+]i) were measured, respectively. RESULTS: SP at a concentration of 10(-5) mol/L caused a significant histamine release with the increase in [Ca2+]i. PP or UVA irradiation alone at doses used in the present study induced no histamine release from mast cells and had no significant effects on SP-induced histamine release from the cells. On the other hand, PP/UVA inhibited SP-induced histamine release in a dose-dependent manner of UVA with the reduction of SP-induced maximal increases in [Ca2+]i. Comparing with the inhibitory effects of PP/UVA on anti-IgE-induced histamine release from IgE-sensitized mast cells and maximal increases in [Ca2+]i in the cells, the inhibitory effects of PP/UVA on the findings in SP-stimulated mast cells were less. CONCLUSION: These data suggest that low doses of PP/UVA inhibits histamine release from SP-activated rat peritoneal mast cells through the suppression of [Ca2+]i.

Inhibition of substance-P-induced histamine release from rat peritoneal mast cells by 8-methoxypsoralen plus long-wave ultraviolet light irradiation: decreased intracellular calcium as a possible mechanism.

Rat peritoneal mast cells purified on a Percoll gradient were activated by substance P (SP) and the effect of 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet light (UVA) irradiation (8-MOP/UVA) on SP-induced histamine release from the cells was investigated. At a concentration of 10(-5) M SP caused a significant histamine release. 8-MOP or UVA irradiation alone at the doses used in the present study neither induced a histamine release nor had any significant effects on SP-induced histamine release from mast cells. On the other hand, 8-MOP/UVA inhibited SP-induced histamine release; this inhibition was dependent on the UVA doses (0.5-3.0 J/cm2) and was accompanied by a reduction in the rise in intracellular calcium concentrations ([Ca2+]i). These data suggest that 8-MOP/UVA inhibits histamine release from SP-activated rat peritoneal mast cells by suppressing the rise in [Ca2+]i.

Inhibition of substance P-induced histamine release from rat peritoneal mast cells by ultraviolet light B irradiation: decreased intracellular calcium as a partial mechanism.

BACKGROUND: Ultraviolet light irradiation has been shown to suppress immunological reactions of irradiated individuals, however, less attention has been paid to the effects on neurogenic inflammation. OBJECTIVE: We have investigated the effect of ultraviolet light B (UVB) irradiation on substance P (SP)-induced histamine release from rat mast cells. METHODS: Rat peritoneal mast cells were treated with UVB irradiation and challenged by SP. Histamine release from the cells and intracellular calcium concentrations ([Ca2+]i) in the cells were measured. RESULTS: UVB irradiation at doses used in the present study did not induce histamine release from mast cells. UVB irradiation at doses from 25 to 200 mJ/cm2 inhibited 10(-5) mol/L SP-induced histamine release in a dose-dependent manner. On the other hand, SP-induced increase of [Ca2+]i was inhibited by UVB irradiation only at doses of 100 and 200 mJ/cm2. CONCLUSION: These data suggest that UVB irradiation inhibits histamine release from SP-activated rat peritoneal mast cells partially through the suppression of an increase in [Ca2+]i.

Histamine in human epidermal cells is induced by ultraviolet light injury.

Human epidermal cell cultures were examined to determine whether they were capable of histamine release. Results of these studies indicated that keratinocytes contain and release significant amounts of histamine. In the skin of some individuals, histamine content was induced after ultraviolet B light injury, and 40% of subjects demonstrated high basal histamine levels. Mass spectrometric analysis of cell supernatants showed that the histamine was released into the extracellular environment. Such release may contribute to common itching or intensify the inflammatory response in vivo.

Effect of a helium-neon laser on cutaneous inflammation.

A Helium-Neon (He-Ne) laser with a wavelength of 632.8 nm is known to have photobiological effects and is widely used for reducing the pain of herpes zoster and accelerating wound healing, however the cellular mechanism and effect of the He-Ne laser are poorly understood. The present study was designed to examine the influence of He-Ne laser irradiation on irritant and allergic contact dermatitis of the mouse ear and on histamine release from rat peritoneal mast cells. Irradiation was applied with a He-Ne laser (12.2 J/cm2) at 1 h, 10 min, 5 min and 0 min before, and 5 min, 6 hs and 24 hs after a challenge of an irritated contact dermatitis (ICD) or allergic contact dermatitis (ACD) was made on the right ears of ICR-mice. Twenty-four hours after the challenge, the swelling of the ear was measured with a dial thickness gauge, and the anti-inflammatory effect of He-Ne laser irradiation was expressed as an ear thickness ratio (ETR). Although the laser did not decelerate the ETR from ICD, the allergic response was decelerated. Irradiation at 5 min after the challenge of contact dermatitis increased the thickness ratio. Next, the influence of the He-Ne laser on histamine release from Wistar-rat peritoneal mast cells was observed. The spontaneous histamine release was inhibited by laser irradiation, while substance P and compound 48/80-induced histamine release were not inhibited. From these results, it can be suggested that He-Ne laser irradiation has an anti-inflammatory effect on cutaneous inflammation.

Histamine-releasing factor(s) in sera of uraemic pruritus patients in a possible mechanism of UVB therapy.

Uraemic pruritus is poorly understood despite the high incidence among chronic renal failure (CRF) patients undergoing haemodialysis. Serum histamine levels have been shown to be elevated in CRF patients with itching, and ultraviolet B (UVB) therapy, even if applied to only part of the body surface, has been reported to be beneficial for the generalized relief of the pruritus. A local mechanism of UVB action is suggested by evidence that UVB radiation is able to suppress histamine release from mast cells. However, detailed systemic mechanism(s) remain obscure. Sera from patients with or without uraemic pruritus were incubated with purified rat peritoneal mast cells and the resulting histamine release was compared. A higher histamine release was obtained with sera from uraemic pruritus patients (44.60 +/- 6.32%, n = 9, P < 0.005) than with sera from patients without itching (19.71 +/- 3.14%, n = 5, P > 0.25) and with normal control sera (23.62 +/- 7.14%, n = 6). This increased histamine release was dose-dependently restored to spontaneous release levels in five of seven patients by pre-exposure of the sera to UVB in vitro. From these results, sera of CRF patients with uraemic pruritus were considered to contain some histamine releasing factor(s) which was depleted or diminished by UVB irradiation, suggesting a possible systemic mechanism of UVB action.

Effect of PUVA radiation on anaphylactic histamine release from rat dermal tissues.

We have devised a new in vitro model of type I cutaneous anaphylaxis. Male albino rats were sensitized with DNP-Ascaris. Abdominal skin was shaved, and thin, split-thickness slices of skin were cut with a dermatome. The dermis was excised and cut into 100 mg pieces. The dermal tissue was incubated with antigen in Tyrode's solution for 30 min at 37 degrees C. Antigen-induced histamine release from dermal tissue was measured fluorimetrically. Using this system, we measured histamine release from PUVA-irradiated and non-irradiated dermal tissues. A single PUVA irradiation inhibited type I cutaneous anaphylaxis, but did not affect spontaneous histamine release or total dermal histamine. Our model is considered to be useful for investigation of the mechanism of suppression of type I cutaneous anaphylaxis by PUVA.

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.