Number Of Intact Mast Cells Research Articles

Differential effects of functionally different histamine H4 receptor ligands on acute irritant dermatitis in mice.

The anti-inflammatory effects of histamine H4 receptor (H4R) antagonists opened new therapeutic options for the treatment of inflammatory/allergic diseases, but the role of H4R in inflammation is far from being solved. Aim of the present study was to investigate the role of structurally related H4R ligands of the aminopyrimidine class with different efficacies and functionalities (neutral antagonist ST-994, partial agonist ST-1006, inverse agonist ST-1012, and partial inverse agonist ST-1124) on croton oil-induced ear edema and pruritus in mice. The H4R ligands were administered subcutaneously before topical application of croton oil. While ST-1006 and ST-1124 were ineffective at any dose tested (10-100 mg/kg), both ST-994 and ST-1012 (30 and 100 mg/kg) significantly reduced croton oil-induced ear edema. Moreover, ST-994, ST-1006, and ST-1124, but not ST-1012, significantly inhibited croton oil-induced ear pruritus at 30 mg/kg. In accordance with results obtained with the reference H4R antagonist JNJ7777120 (100 mg/kg), histological examination of inflamed ear tissue indicated that treatment with ST-994 (30 mg/kg) led to a significant reduction in the inflammatory severity score and in the number of eosinophils infiltrating the tissue, while the number of degranulated mast cells in inflamed tissues was increased in comparison with the number of intact mast cells. These data indicate that croton oil-induced ear inflammation and pruritus seem to be clearly, but variably, affected by the H4R ligands tested. The potential advantage of dual effect of the H4R neutral antagonist ST-994 has to be carefully considered as a new therapeutic approach to the treatment of inflammatory diseases.

Mast cell stabilization and antihistaminic potentials of Curculigo orchioides rhizomes

Aim of the study To investigate the mast cell stabilization and antihistaminic activities of the rhizomes of Curculigo orchioides (COR). Extract of Curculigo orchioides Gaertn. (Fam. Amaryllidaceae) has been reported to possess immunostimulant, and anti-inflammatory potentials. In Indian traditional system of medicine it is also used as anti-asthmatic and anti-inflammatory. Materials and methods Estimation of histamine release is key parameter for evaluating any target for its anti-allergic potential. The stabilization potential of the alcoholic extract of COR (100–400 mg/kg) against mast cell degranulation was studied on isolated mice peritoneal mast cells. The antihistaminic activity was performed by determining the mortality rate of mice upon exposure to compound 48/80 and effect on inhibition of histamine release upon degranulation. Results The raised number of intact mast cells intimates that the COR stabilized the mast cell degranulation (60.96 ± 1.96%) and percentage antihistaminic potential of the extract (63.58 ± 1.8 inhibition at dose of 400 mg/kg) and it virtues further work towards the isolation of phytoconstituents from this plant. Conclusion This finding provides evidence that COR inhibits mast cell-derived immediate-type allergic reactions and mast cell degranulation.

Role of Histamine H3 and H4 Receptors in Mechanical Hyperalgesia following Peripheral Nerve Injury

Objective: Histamine is a chemical mediator that acts at four known types of histamine receptors and has been widely implicated in the development of nociception and neuropathic pain. Blocking histamine H₁ and H₂ receptors has been shown to reduce hyperalgesia following nerve injury, but the role of histamine H₃ and H₄ receptors in neuropathic pain has not been studied. Here, we used blockers of histamine H₃ and H₄ receptors to assess their effects on neuropathic pain behavior and mast cell numbers following peripheral nerve injury. In addition, we assessed the effect of activating H₄ receptors on neuropathic pain behavior. Methods: Rats were subjected to a partial ligation of the sciatic nerve, a model of neuropathic pain, and were treated either systemically or locally (hindpaw) with the H₃/H₄ receptor inverse agonist thioperamide, the specific H₄ receptor antagonist JNJ 7777120, or the H₄ receptor agonist VUF 8430. Measurements of mechanical hyperalgesia were carried out by Randall-Selitto test for 1–3 weeks, and sciatic nerve tissues were analyzed for numbers of intact mast cells by histology at 9 h after surgery. Results: Rats treated with thioperamide or JNJ 7777120 showed significantly enhanced mechanical hyperalgesia after partial ligation of the sciatic nerve. The number of intact mast cells in the injured nerve of these rats was higher than in control rats suggesting reduced mast cell degranulation, but was still significantly lower than in intact nerves. Rats treated with VUF 8430 showed significantly reduced mechanical hyperalgesia. Conclusion: We propose that the increase in mechanical hyperalgesia produced by thioperamide and JNJ 7777120 and the decrease in mechanical hyperalgesia produced by VUF 8430 may represent a direct effect of these agents on mechanospecific primary afferents, or an indirect effect of these agents via injury-induced inflammation.

Effect of Low-Level Laser Therapy on Mast Cells in Second-Degree Burns in Rats

This study sought to investigate whether low-level laser therapy (LLLT) with a helium-neon (He-Ne) laser would affect mast cell number and degranulation in second-degree burns in rats. LLLT has been recently applied to stimulate the wound healing process. Sixty-five rats were randomly allocated to one of five groups. A deep second-degree burn was inflicted on all rats except those in the control group. In the sham-exposed group burns remained untreated. In the two laser-treated groups, the burns were irradiated every day by LLLT, with energy densities of 1.2 and 2.4 J/cm(2). In the fifth group the burns were treated topically with 0.2% nitrofurazone cream every day. The unburned skin of the rats in the control group were used for baseline study. The effects on mast cell number and degranulation were assessed by counting the number of intact and degranulated mast cells in sections fixed in formalin and stained with toluidine blue. On the seventh and 16th days post-burn, the type 1 mast cell count in the 2.4-J/cm(2) laser-treated group was significantly higher than that of the control group. On the 30th day, the total numbers of mast cells in the laser-treated groups were lower than those in the control and sham-exposed groups. LLLT of deep second-degree cutaneous burns in rats significantly increased the number of intact mast cells during the inflammatory and proliferative phases of healing, and decreased the total number of mast cells during the remodeling phase.

Kinetics of eosinophil and IgE-mast cell changes following infection with Angiostrongylus costaricensis in Wistar rats.

Human abdominal angiostrongyliasis is a severe eosinophilic disease caused by Angiostrongylus costaricensis. Previous studies have demonstrated that wild rodents are critically involved as definitive hosts to this nematode in nature. In this study, we have evaluated the susceptibility of Wistar rats (Rattus norvegicus) to A. costaricensis infection. Kinetics of parasitological and pathological changes, including the number of adult worms recovered from mesenteric arteries, and of IgE, mast cell and eosinophil levels in several compartments have been assessed. The oral inoculation of third-stage larvae (L3) into adult Wistar rats led to a marked accumulation of worms in the branches of the mesenteric arteries 25 and 50 days post-inoculation. Intense bone marrow eosinophilia ranging from 7 to 50 days was accompanied by marked accumulation of eosinophils in the blood, peritoneal and bronchoalveolar spaces. Eosinophilic periarteritis, oedema and granuloma in the intestinal and lung tissues were also histologically evident. Total serum IgE and specific anti-parasite IgE peaked at 25 days post-infection, as measured by ELISA and by the passive cutaneous anaphylaxis test, respectively. At that time point, there was a drastic reduction in the number of intact mast cells in the peritoneal effluent. These findings indicate that Wistar rats are permissive to A. costaricensis infection. IgE-mast cell activation and massive tissue eosinophil infiltration are marked features in the process and are likely to play a crucial role in the immune-response evoked by this parasite.

Eotaxin-induced eosinophil migration in the peritoneal cavity of ovalbumin-sensitized mice: mechanism of action.

Cell accumulation in response to i.p. administration of the C-C chemokine, eotaxin, was studied in vivo. OVA-sensitized mice, exhibiting blood eosinophilia, had greater eosinophil (Eø) accumulation in response to 500 ng of eotaxin at 6 h (vehicle-injected, 3.0 +/- 0.5 x 10(5); eotaxin-injected, 8.6 +/- 1.0 x 10(5)) than nonsensitized, eotaxin-injected mice (2.5 +/- 0.4 x 10(5)). A nonspecific neutrophil migration was observed in both vehicle- and eotaxin-injected cavities. The number of intact mast cells in the peritoneal lavages after eotaxin injection was significantly lower than that in vehicle-injected animals (0.8 +/- 0.3 x 10(4) vs 2.8 +/-0.6 x 10(4), respectively). When endogenous peritoneal mast cells were depleted with compound 48/80 before eotaxin administration, there was a 51% reduction in Eø accumulation. This suggests an important role for endogenous mast cells in mediating the actions of eotaxin. The potential role of mast cell mediators in the actions of eotaxin was also investigated. Pretreatment with histamine-H1 or serotonin antagonists reduced Eø migration in response to eotaxin by 50 to 65%. Further, following pretreatment with a specific mAb against TNF-alpha, only nonspecific neutrophil influx was attenuated. Using neutralizing mAbs, Eø migration was found to be dependent on the adhesion molecules P- and E-selectin and CD11b. Eø accumulation was also sensitive to dexamethasone, with doses as low as 0.2 mg/kg inducing 100% inhibition. This study provides useful insight into the mechanisms of action of eotaxin.

Involvement of prostaglandins in the down‐regulation of allergic plasma leakage observed in rats undergoing pleural eosinophilia

1. Recent evidence has implicated eosinophils in the inhibition of allergen-induced rat pleurisy, but the mechanism of this negative modulation is not completely understood. This study was undertaken in order to define the potential role of prostaglandins in this phenomenon. 2. Wistar rats were actively sensitized by subcutaneous injection of a mixture of ovalbumin and AI(OH)3 and challenged with an intrapleural (i.pl.) injection of ovalbumin (12 micrograms/cavity) 14 days later. 3. Analysis of the pleural fluid effluent revealed a massive mast cell degranulation and plasma protein extravasation 4 h post-challenge. We confirmed that concurrently with selective pleural fluid eosinophilia caused by platelet-activating factor (PAF), the pleural cavity became hyporesponsive to allergen-induced protein exudation and to the parallel reduction in the number of intact mast cells. 4. These hyporesponsive animals presented a significant augmentation in the pleural effluent level of prostaglandin E2 (PGE2), which increased with increasing numbers of eosinophils in the pleural cavity. Furthermore, pretreatment with either indomethacin or aspirin failed to modify allergen-induced exudation but reversed the exudatory hyporesponsiveness associated with eosinophil recruitment. 5. Allergic exudation was clearly down-regulated by the following pretreatments: (i) PGE2 (10 micrograms/cavity, i.pl.) plus rolipram (40 micrograms/cavity, i.pl.), (ii) misoprostol (200 micrograms kg-1, p.o.) or (iii) dibutyryl cyclic AMP (80 micrograms/cavity, i.pl.). 6. We conclude that prostaglandins may be implicated in the eosinophil-mediated inhibition of allergic pleurisy, probably acting via cyclic AMP signalling pathway activation.

Interleukin 1 induces a neurally mediated colonic secretion in rats: Involvement of mast cells and prostaglandins

Background/Aims: Interleukin 1β (IL-1β) is known to regulate intestinal ion and water transport in vitro through prostaglandin release. This study investigated the effect of IL-1β on colonic net water flux in vivo to determine its nature (nerve mediation versus action on the epithelium), the mediators involved, and its relationship with mast cell degranulation. Methods: Isolated colonic loops of anesthetized animals were infused with Ringer's buffer containing [14C]polyethylene glycol 4000. Net water flux was calculated according to 14C activity determined in the effluent collected at 15-minute intervals. Histological analysis was used to identify intact mast cells in colonic sections and radioimmunoassay to determine histamine levels. Results: Both IL-1β and the calcium ionophore A23187 induced colonic hypersecretion during 30 minutes. This effect was blocked by tetrodotoxin, doxantrazole, and indomethacin but not chlorpheniramine. Recombinant human interleukin 1β decreased the number of intact mast cells. This effect was eliminated by doxantrazole but not tetrodotoxin or indomethacin. A23187 or IL-1β increased histamine levels in the effluent during 75 and 45 minutes, respectively. Conclusions: In vivo, rhL-1β induces colonic hypersecretion in rats. This effect is nerve mediated but not H1 receptor mediated and involves mast cell degranulation and prostaglandin release.

Mechanical removal of airway epithelium disrupts mast cells and releases granules

Many previous investigators have utilized mechanical rubbing as a method for examining effects of epithelial removal. In the present study, we examined whether this procedure also affects mast cell integrity in the underlying lamina propria. We isolated bronchial rings from six ferrets, and we found that removal of epithelium by rubbing decreased the total number of intact mast cells from 10.0 +/- 1.9 to 2.2 +/- 0.6 (SE) mast cells/mm luminal perimeter (P less than 0.01). In addition, we found a very large number of metachromatic particles that appeared to be mast cell granules unassociated with identifiable mast cells. Their identity was confirmed the presence of free mast cell granules and showed that they contained intact membranes. These effects were not observed when the epithelium was removed by enzymatic digestion, but they were observed after mechanical deformation of the bronchi alone. We suggest that mast cell components released by removing or damaging the epithelium may affect the function of various cells in the airway.

Neurotensin-Induced Mast Cell Degranulation in Human Jejunal Mucosa

The effect of sodium cromoglycate (SCG) on neurotensin- and compound 48/80-induced mast cell degranulation and the effect of combining these secretagogues with each other and with an immunological mast cell degranulation system was studied. Neurotensin reduced the number of intact mast cells from 119 (60-190)/mm2 to 50 (20-101)/mm2. This figure was 76 (34-164)/mm2 when SCG was added to neurotensin, a change that was statistically significant. No such inhibitory effect on mast cell degranulation was seen when SCG was added to compound 48/80, which was active only in high doses. When neurotensin or compound 48/80 was followed by antigen in sensitized tissue specimens, mast cell degranulation was enhanced compared with that taking place with only one of the secretagogues. Neurotensin and compound 48/80 did not cause further mast cell degranulation when applied after IgE followed by antigen or when applied after one another. It is concluded that neurotensin may act through a selective release mechanism, whereas compound 48/80 acts by a cytotoxic mechanism, but that they act on the same group of cells.

Early cellular changes following cryosurgery of oral mucosa in hamsters.

Mitotic activity in the basal epithelial cells and mast cell degranulation have been studied as markers of early cellular change following experimental cryosurgery of hamster sublingual epithelium. It has been shown that mitotic activity initially increases, suggesting that freezing is a stimulus to cell division. Within a short time mitotic activity rapidly falls and this fall is preceded by a marked fall in the number of intact mast cells in the tissue. The timing of both events supports the view that early damage is apparent before vascular stasis intervenes.