Number Of Tryptase-positive Mast Cells Research Articles

Arterial supply and morphological characteristics of sympathetic neurons in the human superior cervical ganglion.

The aim of this study was the micromorphological analysis of the distribution of microvessels, mast cells and ganglionic neurons in two parts, proximal and distal of the human superior cervical sympathetic ganglions (SCSGs). Statistical analyses were applied to detect the possible metric regional differences in their densities. Five injected human SCSGs with colored India ink and gelatin were microdissected and examined. Second group of five human SCSGs was prepared and serially sliced for CD34 and mast cell tryptase immunostaining. The microscopic fields of two parts of the SCSGs were analyzed for the following quantifications: microvessel density (MVD), mast cell density (MCD), and ganglionic cell count and measurements. The mean number of CD34-positive microvessels in microscopic fields, the MVD, had a value of 83 for the upper parts, and 82.7 for the lower parts of SCSGs. The mean number of tryptase-positive mast cells in microscopic fields, the MCD, was 4.5 in the proximal parts, and 4.7 in the distal parts of SCSGs. The mean number of ganglionic neurons in microscopic fields was 19.5 in the proximal parts, and 19.8 in the distal parts of SCSGs. The density of CD34-positive microvessels, the density of tryptase-positive mast cells, and the density, mean diameters and mean areas of ganglionic neurons were not significantly different in two observed parts, upper and lower of the SCSGs. In conclusion, the distributions of microvessels, mast cells, and neurons in two parts of the SCSGs were uniform with no specific micromorphological variations, there is a homogenous vascular and cellular pattern within the SCSGs.

[Discussion of the immunomorphological role of interactions between mast cells and Helicobacter pylori in the gastric mucosa].

Helicobacter pylori induced gastritis accounts for 70% of cases in the structure of this pathology. Features of the long-term inflammatory reaction of the mucous membrane are directly related to the mechanisms of bacterial pathogenicity, and features of immunogenesis within narrow limits of the specific tissue microenvironment of organ structures. Mast cells appear to be one of the key players (promoters) in the regulation of the inflammatory mediator cascade and the formation of cytokine-induced expression. Possessing a wide arsenal of biologically active substances, mast cells are able to participate in the formation of the immune response and resistance of the gastric mucosa, modulating both pro- and anti-inflammatory effects. The antigen-presenting features of mast cells are of interest in terms of interaction with H. pylori and induction of mucosa bacterial colonization. The aim of study was to assess the mast cell tryptase profile of the gastric mucosa in the immunopathogenesis of H. pylori-associated inflammation. Material and methods. The study included 19 biopsies of the gastric mucosa with unknown status of H. pylori infection. Microslides were stained with hematoxylin and eosin, and Giemsa's dye for plain microscopy. H. pylori infection of the gastric mucosa was detected using the immunohistochemical method. Using double immunofluorescent labeling, localization of tryptase-positive mast cells and H. pylori strains was detected. Results. In patients infected with H. pylori (n=12), there was a significant increase in the number of tryptase-positive mast cells (177.99±30.55 vs 88.58±11.49; p<0.05) with activation of secretory pathways and release of protease into the extracellular matrix of the gastric mucosa. The quantitative parameters of mast cells in the group of patients with an undetected pathogen and signs of a chronic inflammation of the gastric mucosa were statistically significantly lower than in the group of infected patients. Co-localization of tryptase-positive mast cells and H. pylori strains (with the formation of areas of large free-lying granule accumulation around the glands with pronounced degree of H. pylori contamination) was detected in gastrobiopsy specimens, the fact evidencing their close involvement in the development of inflammatory reactions of the gastric mucosa. Conclusion. The study demonstrated the features of mast cells and H. pylori interaction revealing previously unknown aspects of gastritis pathophysiology. The data obtained contribute a valuable insight to choose a treatment strategy for H. pylori-associated gastritis.

Tryptase Profile of the Rat Skin Mast Cell Population During the Wound Healing

Mast cells cyclically synthesize and excrete a wide range of biogenesis products with different biological activities into the extracellular matrix and are regulators of local homeostasis both in normal conditions and in pathology – inflammation, oncogenesis, etc. The relative specificity of classical histochemical methods for detecting mast cells in relation to chromogenic to substrates causes certain difficulties in the selective study of the components of the secretome of mast cells, for example, heparin, histamine, chymase or tryptase. Therefore, immunomorphological techniques have become very popular, which identify specific substrates and allow differentiation of the components of the mast cell secretome. Mediators produced by mast cells promote neoangiogenesis, fibrillogenesis and re-epithelialization during the repair process.The aim of our work was to study the tryptase profile of the mast cell population of rat skin during the wound processusing an original combined method of immunohistochemical staining.Material and methods. The experiment involved 12 Wistar rats divided into two groups – intact (n=6) and with the existing wound process of the skin in the withers (n=6). The tryptase profile of mast cells was assessed on the 7th day of the wound process in comparison with the control group.Results. The results obtained showed a significant increase in the number of tryptase-positive mast cells on the 7th day of the wound process in the skin against the background of a general increase in the population of mast cells. Intragranular tryptase reserve was significantly increased. In contrast to the control, where mast cells with single tryptase-positive granules dominated, during the wound process, cells of this type were practically not detected in the skin (43.69±2.9% and 8.55±0.9%). The content of tryptase-positive mast cells with complete filling of the cytoplasm in the control group and the group of animals with a wound process was 14.24±1.2% and 38.03±2.9%, respectively.Conclusion. Thus, when modeling a wound, an increase in tryptase synthesis is detected both in individual MCs and within the entire MC population. This fact indicates that mast cell proteases can become a potential therapeutic target for improving wound regeneration by correcting immunogenesis, inflammation and fiber formation.

Effect of Bone Marrow Autotransplantation on the Numerical Population of Tryptase-Positive Mast Cells, Heparin Sulfation Degree, and Histamine Content.

We studied the effect of bone marrow autotransplantation on the morphofunctional properties and numerical population of mast cells. The experiments were performed on 4-monthold male mice. The animals received an injection of a suspension of bone marrow obtained from the femoral epiphyses of these animals into the caudal vein. In 40 min and 2 h after autotransplantation, the number of tryptase-positive mast cells increased by 1.1 times. The formation of groups of mast cells near erythroid-neutrophil islets and near blood vessels was observed. The proportion of metachromatic mast cells significantly increased. By the degree of mast cells degranulation, we detected non-degranulated up to 48.0±1.4% (vs 55.2±1.2% in intact mice) and moderately degranulated mast cells 22.0±1.2% (vs 18.2±0.9% in intact mice); the percentage of actively degranulated cells was 10.0±0.8% (vs 3.6±0.9% in intact mice; p<0.05). Morphometric parameters of mast cells were changed, with a slight increase in their diameter and distance between the cells. The number of histamine-containing mast cells increased significantly (by 3.2 times in 40 min and by 5.9 times in 2 h) and histamine content in these cells also increased. Thus, bone marrow autotransplantation led to intensification of degranulation and sulfation of mast cells and the release of histamine from them.

[Moxa-stick moxibustion activates mast cells of small intestine tissue in rats].

To explore the effect of moxa-stick moxibustion and joss-stick moxibustion at "Guanyuan" (CV4) on the activity of mast cells in the small intestine tissue in rats. Twelve male SD rats were randomly divided into control, joss-stick moxibustion and moxa-stick moxibustion groups (n=4 rats in each group). Joss-stick or moxa-stick moxibustion was applied to CV4 for 10 min. After moxibustion, the skin temperature of the CV4 region was measured immediately with a thermometer. The mast cells and nerve fibers in the small intestine tissue were displayed by immunofluorescence histochemistry. Compared with the control group, the skin temperature of the CV4 region in both the joss-stick and the moxa-stick groups were significantly increased (P<0.05), while the skin temperature of the moxa-stick group was significantly higher than that in the joss-stick group (P<0.05). There were a large number of tryptase-positive mast cells in the small intestine of rats, some of which were co-expressed with lysosomal-associated membrane protein 1, displaying an activated state. The average numbers of mast cells in the control, joss-stick and moxa-stick groups were 9.2±3.6, 10.8±5.3 and 17.1±6.3, respectively, being significantly higher in the moxa-stick group than in the control and joss-stick groups (P<0.05). In addition, calcitonin gene-related peptide(CGRP) and neuropeptide Y(NPY) positive nerve fibers were found around the mast cells in the small intestinal tissues. Moxa-stick moxibustion gives rise a higher temperature at CV4 to activate mast cells surrounded by CGRP and NPY positive nerve fibers in the small intestine tissue in rats, suggesting an involvement of the sensory and sympathetic nervous system in the activation of intestinal mast cells possibly by way of somatic sympathetic reflex.

Downregulation of iNOS, IL-1β, and P2X7 Expression in Mast Cells via Activation of PAR4 Contributes to the Inhibition of Visceral Hyperalgesia in Rats.

Protease-activated receptor 4 (PAR4) is implicated in the inhibition of visceral hyperalgesia. In the present study, the effects of PAR4 activation on visceral hypersensitivity and expression of inflammatory mediators, including interleukin-1β (IL-1β), P2RX7 purinergic receptor (P2X7), inducible nitric oxide synthase (iNOS), and tryptase, in mast cells (MCs) were investigated via in vivo and in vitro studies. The numbers of tryptase-positive MCs with extensive PAR4, P2X7, and iNOS expression were increased in the colons of visceral hyperalgesia rats compared with controls. Intracolonic administration of PAR4-activating peptide (PAR4-AP) significantly attenuated the visceral hypersensitivity to colorectal distention and reduced the iNOS, IL-1β, P2X7, and tryptase protein and mRNA levels in the colonic mucosa. Treatment of rat bone marrow MCs (BMMCs) with PAR4-AP also reduced the iNOS, IL-1β, P2X7, and tryptase protein and mRNA levels. ERK1/2 and p38 activators (t-butylhydroquinone, tBHQ, and U-46619) reversed the suppressive effect of PAR4 activation on IL-1β and iNOS expression, whereas ERK1/2 and p38 inhibitors (PD98059 and SB203580) reversed the suppressive effect of PAR4 activation on P2X7 and tryptase expression. Our results indicate that the downregulation of inflammatory mediators, including iNOS, IL-1β, P2X7, and tryptase, in MCs that are mediated by PAR4 activation could inhibit visceral hyperalgesia via the mitogen-activated protein kinase (MAPK) signal pathway.

Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells.

Copper has previously been implicated in the regulation of immune responses, but the impact of this metal on mast cells is poorly understood. In this article, we address this issue and show that copper starvation of mast cells causes increased granule maturation, as indicated by higher proteoglycan content, stronger metachromatic staining, and altered ultrastructure in comparison with nontreated cells, whereas copper overload has the opposite effects. In contrast, copper status did not impact storage of histamine in mast cells, nor did alterations in copper levels affect the ability of mast cells to degranulate in response to IgER cross-linking. A striking finding was decreased tryptase content in mast cells with copper overload, whereas copper starvation increased tryptase content. These effects were associated with corresponding shifts in tryptase mRNA levels, suggesting that copper affects tryptase gene regulation. Mechanistically, we found that alterations in copper status affected the expression of microphthalmia-associated transcription factor, a transcription factor critical for driving tryptase expression. We also found evidence supporting the concept that the effects on microphthalmia-associated transcription factor are dependent on copper-mediated modulation of MAPK signaling. Finally, we show that, in MEDNIK syndrome, a condition associated with low copper levels and a hyperallergenic skin phenotype, including pruritis and dermatitis, the number of tryptase-positive mast cells is increased. Taken together, our findings reveal a hitherto unrecognized role for copper in the regulation of mast cell gene expression and maturation.

Distribution, subtype population, and IgE positivity of mast cells in chronic rhinosinusitis with nasal polyps

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) has been categorized into 2 subtypes in the Asian population: eosinophilic chronic rhinosinusitis (ECRS; similar to CRSwNP in Western countries) and non-ECRS (characterized by inflammation dominated by T-helper cell type 1). The pathogenesis of CRSwNP and the role of mast cells are poorly understood. ObjectiveTo investigate the distribution, phenotypes, and immunoglobulin E (IgE) positivity of mast cells in these 2 subtypes of CRSwNP. MethodsWe collected nasal tissue from patients with CRSwNP and control subjects. The mRNA for mast cell proteases tryptase and chymase was measured using real-time polymerase chain reaction, and the distribution of each type of protease-positive mast cell was examined using immunohistochemistry and immunofluorescence. IgE distribution on mast cells was determined using double-immunofluorescent staining for IgE and tryptase. ResultsExpression of tryptase mRNA was significantly increased in nasal polyps from patients with the 2 subtypes of CRSwNP compared with controls. Immunohistochemistry showed increased numbers of tryptase-positive mast cells in the epithelium, glands, and submucosa of ECRS polyps, whereas the number of tryptase- and chymase-positive mast cells was increased in the glands and submucosa of non-ECRS polyps. IgE-positive mast cells were abundant in the epithelial, glandular, and submucosal regions of ECRS polyps but few were detected in non-ECRS polyps. ConclusionThe present study demonstrates that the distribution, subtype population, and IgE positivity of mast cells is different between ECRS and non-ECRS nasal polyps. Our results suggest a role for IgE-mediated mast cell activation in the pathogenesis of ECRS.

Siramesine causes preferential apoptosis of mast cells in skin biopsies from psoriatic lesions.

Skin mast cells are implicated as detrimental effector cells in various inflammatory skin diseases such as contact eczema, atopic dermatitis and psoriasis. Selective reduction of cutaneous mast cells, e.g. by inducing targeted apoptosis, might prove a rational and efficient therapeutic strategy in dermatoses negatively influenced by mast cells. The objective of the present study was to evaluate whether a lysosomotropic agent such as siramesine can cause apoptosis of mast cells present in psoriatic lesions. Punch biopsies were obtained from lesional and uninvolved skin in 25 patients with chronic plaque psoriasis. After incubation with siramesine, the number of tryptase-positive mast cells and their expression of interleukin (IL)-6 and IL-17 was analysed. Skin biopsies were digested to allow flow cytometric analysis of the drug's effect on cutaneous fibroblasts and keratinocytes. Siramesine caused a profound reduction in the total number of mast cells in both lesional and uninvolved psoriatic skin biopsies without affecting the gross morphology of the tissue. The drug reduced the density of IL-6- and IL-17-positive mast cells, and showed antiproliferative effects on epidermal keratinocytes but had no apparent cytotoxic effect on keratinocytes or dermal fibroblasts. Considering the pathophysiology of psoriasis, the effects of siramesine on cutaneous mast cells may prove favourable from the therapeutic aspect. The results encourage further studies to assess the usefulness of siramesine and other lysosomotropic agents in the treatment of cutaneous mastocytoses and inflammatory skin diseases aggravated by dermal mast cells.

5 nm Silver Nanoparticles Amplify Clinical Features of Atopic Dermatitis in Mice by Activating Mast Cells.

The triggering effect of silver nanoparticles (NPs) on the induction of allergic reactions is evaluated, by studying the activation of mast cells and the clinical features of atopic dermatitis in a mouse model. Granule release is induced in RBL-2H3 mast cells by 5 nm, but not 100 nm silver NPs. Increases in the levels of reactive oxygen species (hydrogen peroxide and mitochondrial superoxide) and intracellular Ca++ in mast cells are induced by 5 nm silver NPs. In a mouse model of atopic dermatitis induced by a mite allergen, the skin lesions are more severe and appear earlier in mice treated simultaneously with 5 nm silver NPs and allergen compared with mice treated with allergen alone or 100 nm silver NPs and allergen. The histological findings reveal that number of tryptase-positive mast cells and total IgE levels in the serum increase in mice treated with 5 nm silver NPs and allergen. The results in this study indicate that cotreatment with 5 nm silver NPs stimulates mast cell degranulation and induces earlier and more severe clinical alterations in allergy-prone individuals.

Analysis of tryptase-positive mast cells and immunoexpression of MMP-9 and MMP-13 in periapical lesions.

To evaluate the immunoexpression of tryptase, MMP-9 and MMP-13 in periapical lesions, correlating them with the type of lesion, intensity of the inflammatory infiltrate and thickness of the epithelial lining. Twenty periapical granulomas (PGs), twenty radicular cysts (RCs) and twenty residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using antitryptase, anti-MMP-9 and anti-MMP-13 antibodies. Immunoexpression of MMP-9 and MMP-13 was quantitatively evaluated both in the connective tissue of all lesions and in the epithelial lining of RCs and RRCs. Tryptase-positive mast cells were counted only in the connective tissue. The data were analysed using Kruskal-Wallis and Fisher's exact tests, as well as Spearman's correlation test (P<0.05). In comparison with RCs and RRCs, PGs exhibited higher immunoexpression of tryptase, MMP-9 and MMP-13 (P=0.002, P = < 0.001 and P<0.001, respectively). In comparison with lesions with inflammatory infiltrates grades I and II, lesions with inflammatory infiltrate grade III had higher median percentages of MMP-13-positive cells (P=0.003) and a tendency for higher expression of MMP-9 (P=0.059). No significant difference was observed between the expression of the studied markers and epithelial thickness (P>0.05). There were positive correlations between the number of tryptase-positive mast cells and the immunoexpression of MMP-9, as well as between the immunoexpression of MMP-9 and MMP-13. A larger number of tryptase-positive mast cells and greater enzymatic activity of MMP-9 and MMP-13 were found in PGs compared to RCs and RRCs. These findings are a characteristic of the dynamics of periapical diseases.

Tu1795 Increased Number of Tryptase-Positive Mast Cells in the Colonic Mucosa of IBS Patients in Mexico and Its Relation With Perceived Stress

Tu1795 Increased Number of Tryptase-Positive Mast Cells in the Colonic Mucosa of IBS Patients in Mexico and Its Relation With Perceived Stress

Mast cells infiltration and decreased E-cadherin expression in ketamine-induced cystitis

BackgroundKetamine is a controlled substance and often illegally used as a recreational drug primarily by young adults. Increasing ketamine abusers associated with lower urinary tract symptoms have been reported at hospitals in recent years. Here we used a murine model to explore the changes of bladder in order to elucidate its pathogenesis. MethodsICR mice were randomly distributed into control and ketamine groups and received daily intraperitoneal injection of saline and ketamine (30mg/kg), respectively. The bladders were excised and processed for histology at 4, 8 and 12 weeks. Tryptase and E-cadherin were investigated by immunohistochemistry in bladder tissues from ketamine-treated and control mice to assess the mast cell activation and junction protein expression. ResultsAfter ketamine treatment, the bladder changed to be hyperemic, inflamed, and with more fissures in mucosa. Compared with control group, the number of tryptase-positive mast cells significantly increased, which was 6.98±2.89 and 23.00±6.48cells per field (100×) at 8 and 12 weeks, respectively (P=0.016 and P=0.003, respectively). Additionally, the expression of E-cadherin in ketamine-treated mice bladder tissue was significantly lower than that in the control tissues, P<0.001. ConclusionsIncreased mast cells in bladder wall and downregulated expression of E-cadherin junction protein in epithelial cells were probably associated with interstitial inflammation and fissures in mucosa. It implied that ketamine induced an interstitial cystitis.

Increased Numbers of Tryptase-Positive Mast Cells in the Healthy and Sun-Protected Skin of Tobacco Smokers

Background: Tobacco smoking may cause skin aging through mast cell proteinases. Objective: To compare the numbers of mast cells showing tryptase and chymase in the healthy-looking skin of smokers and non-smokers. Methods: The study subjects consisted of 80 males, 42 of whom were smokers and 38 non-smokers. A skin biopsy from the medial arm was processed for immunohistochemical staining of tryptase and chymase, as well as chymase inhibitors alpha-1-proteinase inhibitor (alpha-1-PI) and alpha-1-antichymotrypsin (alpha-1-AC). Results: The number of tryptase⁺ mast cells was significantly higher in the smoker group (84 ± 32 cells/mm²) than in the non-smoker group (70 ± 32 cells/mm²) (p = 0.044). Likewise, the number of chymase⁺ mast cells was higher in the smoker group (89 ± 20 vs. 80 ± 22 cells/mm²), though statistical significance was not reached (p = 0.07). No significant difference was observed in alpha-1-PI⁺ and alpha-1-AC⁺ cells. Conclusion: Especially tryptase, but probably also chymase, may have an influence on the skin of smokers, such as wrinkling and aging.

An assessment of mast cells and myofibroblasts in denture‐induced fibrous hyperplasia

The pathogenesis of denture-induced fibrous hyperplasias has not been examined in detail to explain how tissue injury results in fibrous hyperplasia of the oral mucosa. We examined the presence of mast cells and myofibroblasts in 33 denture-induced fibrous hyperplasias (DIFH) compared with 10 healthy gingival tissues. The parameters examined included mast cell numbers, tissue distribution, degranulation, and cell subtypes using immunohistochemistry. The presence of myofibroblasts and their likely origin was also examined by double immunofluorescense staining. Furthermore, we investigated the synthesis of osteopontin and TGF-β, considered to be involved in the transformation of a fibroblast to a myofibroblast. The results demonstrated that the mast cell numbers are significantly increased in the DIFH compared with non-disease controls. The mast cell localization in lesions was higher in the superficial areas with inflammatory cell infiltration compared with the deep fibrotic area (P < 0.01). The number of tryptase-positive mast cells was significantly higher compared with chymase-positive ones. The TGF-β- or osteopontin-positive cell infiltration into the lesion was found in high numbers. The presence of myofibroblasts was identified in 14 of 33 cases (42%), and some of these cells showed apoptosis when assessed by the TUNEL assay. On the survey of the origin of myofibroblasts, results showed αSMA and vimentin positivity indicating these transformed from fibroblasts. These results are the first to show that mast cells and myofibroblasts can be detected in DIFH, indicating important roles of these cells in the pathogenesis of this lesion.

Effects of sugammadex and rocuronium mast cell number and degranulation in rat liver

We investigated the effect of rocuronium- and sugammadex-induced mast cell increase and degranulation in rat portal triads. Forty-two rats, in six groups, received either rocuronium 1 mg.kg(-1); sugammadex 15 mg.kg(-1); sugammadex 100 mg.kg(-1); rocuronium 1 mg.kg(-1) and 5 min later, sugammadex 15 mg.kg(-1); rocuronium 1 mg.kg(-1) and 5 min later, sugammadex 100 mg.kg(-1); or isotonic saline. Total mast cell numbers were significantly higher with rocuronium only, than in all other groups (p<0.003), although in all active groups, the number was greater than the control. Total mast cell number was significantly higher with rocuronium and low-dose sugammadex compared with low-dose sugammadex only. The number of tryptase-positive mast cells with rocuronium only was significantly higher than in all other groups (p<0.003). Tryptase-positive mast cell numbers in both groups receiving both rocuronium and sugammadex were significantly higher compared with both groups receiving sugammadex only. Rocuronium increased mast cell numbers, and degranulation was mitigated by sugammadex. These results suggest that sugammadex may be beneficial in treatment of rocuronium-induced anaphylaxis.

Mast cells in human testicular biopsies from patients with mixed atrophy: increased numbers, heterogeneity, and expression of cyclooxygenase 2 and prostaglandin D2 synthase

To determine intratesticular abundance and distribution of tryptase-positive mast cells (MCs) and to examine the expression of key enzymes of prostaglandin (PG) synthesis, cyclooxygenase 2 (COX2), and PGD2 synthase in the testes of men with mixed atrophy (MA) syndrome and in normal samples. Retrospective study. Academic research institute and andrology practice. Nineteen men. Testicular biopsies. Immunohistochemistry and evaluation of COX2 and tryptase-positive MCs, laser microdissection of immunoreactive cells followed by reverse transcriptase polymerase chain reaction for COX2 and PGDS-H mRNA, and transmission electron microscopy. In line with previous studies, few tryptase-positive MCs, but no COX2-positive cells, were observed in testes with normal spermatogenesis. In MA samples, the number of tryptase-positive MCs was significantly increased and the cells accumulated in the walls of the seminiferous tubules. In 11 of 13 MA samples, COX2 protein was detected. In 2 cases, Leydig cells were positive; however, in all 11 of 13 cases, COX2 was localized to MCs, coexpressing tryptase. The proportion of MCs coexpressing COX2 varied from 4% to 35%. Laser microdissection of tryptase/COX2-positive MCs followed by reverse transcriptase polymerase chain reaction revealed PGDS-H mRNA. Transmission electron microscopy identified typical MCs with abundant granules and another subtype with only a few granules, implying that MCs may differentiate in the testes. In patients with MA, testicular MC numbers and phenotypes change with respect to the ability to express COX2 and synthesize PGs. MCs and PGs have emerged as players in spermatogenic dysfunction.

Indications of ‘atopic bowel’ in patients with self‐reported food hypersensitivity

An association between atopic disease and gastrointestinal complaints has been suggested. To explore the association between atopic disease, gastrointestinal symptoms, and possible gastrointestinal manifestations of atopic disease in patients with self-reported food hypersensitivity. Symptoms, skin prick tests, serum markers of allergy and intestinal permeability were recorded in 71 adult patients. Eosinophils, tryptase- and IgE-positive cells were counted in duodenal biopsies. Sixty-six (93%) patients had irritable bowel syndrome (IBS) and 43 (61%) had atopic disease, predominantly rhinoconjunctivitis. All 43 were sensitized to inhalant allergens, 29 (41%) to food allergens, but food challenges were negative. Serum total IgE and duodenal IgE-positive cell counts were significantly correlated (P < 0.0001) and both were significantly higher in atopic than in non-atopic patients (P < 0.0001 and P = 0.003 respectively). IgE-positive cells appeared to be 'armed' mast cells. Intestinal permeability was significantly elevated in atopic compared with non-atopic patients (P = 0.02). Gastrointestinal symptoms and numbers of tryptase-positive mast cells and eosinophils did not differ between groups. Patients with self-reported food hypersensitivity had a high prevalence of IBS and atopic disease. Atopic patients had increased intestinal permeability and density of IgE-bearing cells compared with non-atopic patients, but gastrointestinal symptoms did not differ between groups.

Angiogenesis and mast cells in human breast cancer sentinel lymph nodes with and without micrometastases

An increasing number of mast cells have been reported in angiogenesis associated with solid and haematopoietic tumours. Data concerning the number of mast cells in neoplastic lymph nodes and their relationship with microvessel density are controversial. The aim was to correlate the extent of angiogenesis with the number of mast cells reactive with tryptase in biopsy specimens of sentinel lymph nodes with and without micrometastases obtained from patients with breast cancer. Specimens from sentinel lymph nodes obtained from 80 patients (40 with and 40 without micrometastases) were investigated immunohistochemically by using anti-CD31 and anti-tryptase antibodies. Angiogenesis, measured as microvessel counts, increased in parallel with the number of tryptase-positive mast cells and their values were significantly higher in lymph nodes with micrometastases compared with those without. Tryptase-positive mast cells may contribute, at least in part, to angiogenesis occurring in sentinel lymph nodes with micrometastases from patients with breast cancer.

Possible involvement of mast cells in renal fibrosis in patients with IgA nephropathy

The objective of the present study is to investigate whether human mast cells (MC) contribute to renal damage through local activation of the renin-angiotensin system, by assessing their numbers in renal biopsy specimens from patients with IgA nephropathy (IgAN) or minimal change nephrotic syndrome (MCNS). In patients with IgAN and MCNS, the numbers of tryptase-positive MC (MC(T)) and MC positive for both tryptase and chymase (MC(TC)) were examined histopathologically. Serum creatinine level, mean blood pressure and the severity of glomerular and tubulointerstitial lesions were also determined. MC(TC) numbers differed between IgAN patients and MCNS patients. IgAN patients had more MC(TC) than MC(T). MC were found around but not in the conglomerate of the AngiotensinII (AngII)-positive cells. In the IgAN patients with the most severe pathology, the number of AngII-positive cells was correlated with that of MC(TC) and MC(T). Chymase-dependent AngII synthesis due to human MC may be involved in the inflammatory and fibrotic processes of IgAN.