Mast Cells

The areas of 2327 mast cell granules in transmission electron micrographs of sections of peritoneal mast cells from adult rats were measured by digitized planimetry. A histogram constructed using equivalent volumes calculated from the measured areas assuming approximation of the granules to spheres showed a periodic multimodal distribution in which the modes fell at volumes that were successively larger integral multiples of the volume at the first mode. Application of a moving-bin technique to the data confirmed the presence of the modes. We propose a mechanism of fusion of unit sized granules to account for the multimodal distribution. The presence of pear-and dumbbellshaped granules in mast cells is consistent with this mechanism.

Kyungohkgo (KOG) is one of the most important formulas in traditional oriental medicine. We investigated the remedial effect of KOG on the development of atopic dermatitis (AD) in female NC/Nga mice. AD-like lesion was induced by the application of 2,4-Dinitrochlorobenzene on to the back skin repeatedly; KOG was administered orally (12.5 and 25.0 mg/kg) and topically (0.5 and 1.0 mg/mouse) to NC/Nga mice once a day for all through the period of this experiment and every mouse body weight was periodically taken. The effects of KOG on 2,4-Dinitrochlorobenzene-treated NC/Nga mice were determined by measuring AD-like skin lesions, the infiltration of mast cells and serum immunoglobulin E concentration. After the KOG applications are over, the KOG groups had less skin lesions than the atopy one, their immunoglobulin E levels were significantly downregulated and the infiltration of mast cells in the dorsal skin were reduced. Our results suggest that KOG may be effective in alleviating the development of AD. The inhibition of AD in NC/Nga mice may be influenced by the prevention of mast cell activation.

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.

The participation of mast cells in connective tissue repair was studied using the perforated-rat-mesentery model. Perforation of mesenteric membranes was performed during laparotomy of anesthetized Sprague-Dawley rats. Laparotomy significantly reduced the histamine content of the mesenteric membranes on day 1 postoperatively and perforation as such reduced the histamine content even more on days i-10. Mast cell activation induced by a single intraperitoneal injection of Compound 48/80 two days prior to operation, significantly improved healing on days 5 -7 postoperatively. Daily injections of Compound 48/80 for 5 days prior to operation showed significantly better healing compared to such injections for five days postoperatively. Administration of lupitidine, a long acting histamine H2-rece ptor antagonist, two times daily starting on the day of 48/80 injection to day 4 after operation did not apparently affect healing.

Mast cells are mobile granule-containing secretory cells that are distributed preferentially about the microvascular endothelium in oral mucosa and dental pulp. The enzyme profile of mast cells in oral tissues resembles that of skin, with most mast cells expressing the serine proteases tryptase and chymase. Mast cells in oral tissues contain the pro-inflammatory cytokine tumour necrosis factor-α in their granules, and release of this promotes leukocyte infiltration during evolving inflammation in several conditions, including lichen planus, gingivitis, pulpitis, and periapical inflammation, through induction of endothelial-leukocyte adhesion molecules. Mast cell synthesis and release of other mediators exerts potent immunoregulatory effects on other cell types, while several T-lymphocyte-derived cytokines influence mast cell migration and mediator release. Mast cell proteases may contribute to alterations in basement membranes in inflammation in the oral cavity, such as the disrupti...

BAKER D. G., GERSHWIN L. J. and HYDE D. M. 1993. Cellular and chemical mediators of type 1 hypersensitivity in calves infected with Ostertagia ostertagi: mast cells and eosinophils. International Journal for Parasitology 23: 327-332. Abomasal mucosal mast cell and eosinophil accumulation was morphometrically evaluated in 26 Holstein steers after natural or experimental infection with Ostertagia ostertagi. Results showed that following infection, accumulation of mast cells and eosinophils in abomasal tissue was dependent on infection pattern. Eosinophilia was greater in steers with type 1 ostertagiosis, while mastocytosis was more pronounced in steers with type 2 ostertagiosis. INDEX KEY WORDS: Ostertagia ostertagi; cattle parasites; mast cell; eosinophil; morphometry; type 1 hypersensitivity.

Endometriosis is a continuous and progressive disease with a poorly understood aetiology, pathophysiology and natural history. This study evaluated the histological differences between eutopic and ectopic endometria (abdominal wall endometriosis) and the expression of mast cell proteases (tryptase and chymase), annexin A1 (ANXA1) and formyl peptide receptor 1 (FPR1). Ectopic endometrium from 18 women with abdominal wall endometriosis and eutopic endometrium from 10 women without endometriosis were obtained. The endometrial samples were analysed by histopathology, immunohistochemistry and ultrastructural immunogold labeling to determine mast cell heterogeneity (tryptase and chymase positive cells) and the expression levels of ANXA1 and FPR1. Histopathological analysis of the endometriotic lesions showed a glandular pattern of mixed differentiation and an undifferentiated morphology with a significant influx of inflammatory cells and a change in mast cell heterogeneity, as evidenced by a significant increase in the number of chymase-positive cells and endogenous chymase expression. The undifferentiated glandular pattern of endometriotic lesions was positively associated with a marked increase and co-localization of ANXA1 and FPR1 in the epithelial cells. In conclusion, the co-upregulated expression of mast cell chymase and ANXA1-FPR1 system in ectopic endometrium suggests their involvement in the development of endometriotic lesions.

In patients given a diagnosis of chronic spontaneous urticaria (CSU), there are no obvious external triggers, and the factors that initiate the clinical symptoms of wheal, flare, and itch arise from within the patient. Most patients with CSU have an autoimmune cause: some patients produce IgE autoantibodies against autoantigens, such as thyroperoxidase or double-stranded DNA, whereas other patients make IgG autoantibodies against FcεRI, IgE, or both, which might chronically activate mast cells and basophils. In the remainder of patients with CSU, the nature of the abnormalities has not yet been identified. Accumulating evidence has shown that IgE, by binding to FcεRI on mast cells without FcεRI cross-linking, can promote the proliferation and survival of mast cells and thus maintain and expand the pool of mast cells. IgE and FcεRI engagement can also decrease the release threshold of mast cells and increase their sensitivity to various stimuli through either FcεRI or other receptors...

Psoriasis is considered an immune chronic disease in which T cells are accepted as important. Nowadays, it is believed that psoriasis is most likely a T helper (Th)1/Th17 induced inflammatory disease. However, some other cells, such as endothelial cells, dendritic cells, monocytic cells, neutrophils, keratinocytes, and several cytokines, appear to have, at different stages of the disease, an important role in its pathogenesis. For instance, the response to psoriasis therapy is dependent not only on the inactivation of Th1 and Th17 immune responses but also on the inactivation of dendritic cell products. Moreover, interleukin (IL)-23 deregulation appears to be an independent factor in the pathogenesis of psoriasis. Indeed, currently, the IL-23/Th17 axis is believed to be crucial in psoriasis pathogenesis, and its inhibition appears to be important for therapeutic achievement. This review presents the roles and interactions of cells and cytokines that are related to psoriasis pathogenesis.

Although the use of tanniferous plants or condensed tannins as an alternative to anthelmintics to control gastrointestinal nematodes has been largely documented in sheep, studies remain scarce in goats. The objective of this study was therefore to assess the possible impact of condensed tannins in goats infected with adult Haemonchus contortus. Two groups of cull goats were experimentally infected with 10.000 L3 of H. contortus. After 4 weeks, quebracho extracts, representing 5% of the diet DM, were administered for 8 days to one of the two groups. Goats of the second group remained as controls. One week after the end of quebracho administration, the goats were euthanised. Individual egg excretion and pathophysiological parameters were measured weekly during the study. At the end of the study, worm counts were assessed and histological samples from the abomasa were taken to count the numbers of mucosal mast cells, globule leukocytes and eosinophils. The administration of tannins was associated with a significant decrease in egg excretion, which persisted until the end of experiment. This reduction was not associated with any difference in worm number but with a significant decrease in female fecundity. No significant changes in the mucosal density of the three inflammatory cell types were detected between the two groups. These results indicate that the major consequence of tannin consumption in goats is a reduction in worm fecundity and egg output, which does not seem related to significant changes in the local mucosal response.

Objective and design: To investigate the severity and duration of colitis induced by two different doses of 2,4,6-trinitrobenzenesulfonic acid (TNBS) and the changes in mast cell number in acute infl ammation and in the recovery process of colitis. Methods: Colitis was induced in rats by an enema of TNBS (10 or 30 mg) in 25 % ethanol. Macroscopic and histologic changes of the colon, colon weight and mast cell counts were examined at various times (7, 30 and 60 days) after colitis induction. Results: TNBS induced a colonic damage which was doserelated for both severity and time necessary to complete recovery. On day 7 after colitis induction 10 mg TNBS induced macroscopic and microscopic alterations of colonic architecture that completely resolved at day 60. By contrast, 30 mg TNBS induced massive necrosis, thickening of the colon, severe histologic changes that were only partially reversed after two months. Mast cell number in the submucosa and muscularis propria decreased signifi cantly in the acute phase of infl ammation (7 days) and slowly increased thereafter, reaching a maximum level (up to about 5-fold) at day 60 after both doses of TNBS. Conclusions: Present data confi rm the ability of TNBS to induce in rats damage to the colon that was dose-dependent for severity and duration. Moreover, these data unravel a different role of mast cells in TNBS-induced colitis: an early degranulation in the acute phase of infl ammation and a subsequent accumulation of mast cells in the late phase of the disease, associated with tissue repair.

Background Novel approaches are being explored to develop new therapies for various allergic diseases. Complementary and alternative medicines are considered to be promising avenues for the development of such new therapies. Objectives To investigate the effect of many Korean plants on the IgE-mediated allergic response in mast cells and in vivo, and its mechanism of action. Materials and methods The anti-allergic activity was tested by evaluating effects on degranulation of mast cells in culture and passive cutaneous anaphylaxis (PCA) in vivo. Its mechanism of action was investigated by immunoblotting analysis, immunoprecipitation, RT-PCR, and other molecular biological approaches in mast cells.

The small chemical vacuolin-1 induces rapid formation of large vacuoles in various cell types. In epithelial cells, vacuolin-1 has been shown to inhibit Ca 2+ ionophore-induced exocytosis depending on experimental conditions used but had no effect on repair of damaged membranes. However, it is not known whether vacuolin-1 could inhibit exocytosis induced by immunoreceptor triggering in professional secretory cells and whether there is any correlation between effect of vacuolin-1 on exocytosis and membrane repair in such cells. Here we show that in rat basophilic leukemia (RBL-2H3) cells activated by the high-affinity IgE receptor (FcεRI) triggering vacuolin-1 enhanced exocytosis. Under identical conditions of activation, vacuolin-1 inhibited exocytosis in mouse bone marrow-derived mast cells (BMMCs). This inhibition was not reflected by decreased phosphorylation of the FcεRI α and β subunits, linker for activation of T cells, non-T cell activation linker, Akt and MAP kinase Erk, and uptake of extracellular Ca 2+ , indicating that early activation events are not affected. In both cell types vacuolin-1 led to formation of numerous vacuoles, a process which was inhibited by bafilomycin A1, an inhibitor of vacuolar H + -ATPase. Thapsigargin-or Ca 2+ ionophore A23187induced exocytosis also showed different sensitivity to the inhibitory effect of vacuolin-1. Pretreatment of the cells with vacuolin-1 followed by permeabilization with bacterial toxin streptolysin O enhanced Ca 2+dependent repair of plasma membrane lesions in RBL-2H3 cells but inhibited it in BMMCs. Our data indicate that lysosomal exocytosis exhibits different sensitivity to vacuolin-1 depending on the cell type analyzed and mode of activation. Furthermore, our results support the concept that lysosomal exocytosis is involved in the repair of injured plasma membranes.

Recent clinical studies have brought asthma's complex inflammatory processes into clearer focus, and understanding them can help to delineate therapeutic implications. Asthma is a chronic airway inflammatory disease characterized by the infiltration of airway T cells, CD + (T helper) cells, mast cells, basophils, macrophages, and eosinophils. The cysteinyl leukotrienes also are important mediators in asthma and modulators of cytokine function, and they have been implicated in the pathophysiology of asthma through multiple mechanisms. Although the role of eosinophils in asthma and their contribution to bronchial hyperresponsiveness are still debated, it is widely accepted that their numbers and activation status are increased. Eosinophils may be targets for various pharmacologic activities of leukotriene receptor antagonists through their ability to downregulate a number of events that may be key to the effector function of these cells. (J Allergy Clin Immunol 2003;111:S5-17.)

Autoimmunity is a disease that occurs when the body tissue is attacked by its own immune system. Multiple sclerosis (MS) is an autoimmune illness which triggers neurological progressive and persistent functions. MS is associated with an abnormal B-cell response and upregulation of T-cell reactivity against a multitude of antigens. Mast cells are the first line of the innate immune system and act by de-granulating and secreting chemical mediators and cytokines. Their participation on the central nervous system has been recognized since the beginning of the last century. They have an important role in autoimmune disease, including MS where they mediate inflammation and demyelinization by presenting myelin antigens to T cells or disrupting the blood–brain barrier and permitting entry of inflammatory cells and cytokines. The participation of mast cells in MS is demonstrated by gene overexpression of chemical mediators and inflammatory cytokines. Here we report the relationship and involvement between mast cells and multiple sclerosis.

In contrast to the roles played by monocytes/macrophages, neutrophils and lymphocytes, the presence and functions of basophils, mast cells/eosinophilic granule cells, eosinophils and rodlet cells in teleosts are areas of controversy. The tissue distribution of mast cells/eosinophilic granule cells in species from a certain genus shows a characteristic pattern, and this pattern is usually also present at the family level. Functionally, the mast cells/eosinophilic granule cells of teleosts show close similarity to the mast cells of mammals. Acute tissue damage is causing mast cell/eosinophilic granule cell degranulation and release of mediators of inflammation, whereas an increase in the number of these cells is often found in chronically inflamed tissues. The mast cells/eosinophilic granule cells of teleosts show marked diversity in their staining properties, with both basophilic and acidophilic components in their granules. In some fish families, e.g. the labrids, the eosinophilic component is dominating, whereas in the pike the granules are strongly basophilic and show the metachromatic staining characteristics found in the granules of mast cells, but being more akin to the granules of the mucosal than to those of the connective tissue type of mast cells of mammals. With respect to rodlet cells, a cell type hitherto clearly demonstrated only in teleosts, a characteristic distribution pattern seems to be established in certain families. In other families rodlet cells are absent in some individuals and present in different tissues in others. However, there is a close relation between the presence of helminths or other noxious agents and the presence of rodlet cells. Massive aggregations of such cells can be seen in affected epithelia of gills or the intestinal tract, and in individuals of species from some fish families they also occur in association with mesothelial and endothelial tissues. The rodlet cell may represent a type of eosinophilic granulocyte that populates the tissues at its immature stage and mature in response to the appropriate stimuli, in a way similar to that of mast cell precursors. Present evidence points to a functional role for the rodlet cells of teleosts in host defence against parasites.

This work describes recent results from our research program aiming at the synthesis and evaluation of new compounds acting as potential anti-inflammatory drugs. A series of novel acyl-hydrazones bearing 2-aryl-thiazole moiety were synthesized by the condensation between derivatives of 4-[2-(4-methyl-2-phenyl-thiazole-5-yl)-2-oxo-ethoxy]-benzaldehyde and 2, 3 or 4-(2-aryl-thiazol-4-ylmethoxy)-benzaldehyde, respectively and different carboxylic acid hydrazides. The structures of newly synthesized compounds were established by the combined use of IR, (1)H NMR, mass spectral data and elemental analysis. These compounds were tested in vivo for their anti-inflammatory activity, in an acute experimental inflammation. The acute phase bone marrow response, phagocytes' activity and NO synthesis were evaluated. Compounds 10, 15, 17, 18 and 22 reduced the absolute leukocytes count due to the lower neutrophils percentage. Phagocitary index was decreased by all the compounds. Seven of them r...

The cell line HMC-1, derived from a patient with mast cell leukaemia, is the only established cell line exhibiting a phenotype similar to that of human mast cells. This paper reports on a detailed characterization of the expression of a panel of markers for various types of immature and mature haematopoietic cells in the HMC-1. We also studied the potential of HMC-1 to differentiate upon treatment with conditioned media from the human T-cell line Mo, retinoic acid or DMSO. HMC-1 was found to express several mast cell-related markers. A high expression of Kit, the receptor for stem-cell factor, was detected. The majority of the cells were stained with a MoAb against the mast cell-specific serine protease tryptase. Of particular interest was the finding that beta-tryptase mRNA, but not alpha-tryptase mRNA, was expressed in HMC-1. Using enzyme-histochemistry we were able to show that the beta-tryptase was enzymatically active, indicating that tryptase can form active homotetramers. Bot...

Melasma is an acquired hypermelanosis on sun-exposed areas. Its pathogenesis has not been clearly elucidated. Using histochemistry (Giemsa, Verhoeff–van Gieson and Fontana–Masson staining), we evaluated melasma lesions and compared them with nonlesional skin. Skin samples were obtained from lesional and nonlesional facial skin of 27 patients with melasma, and biopsies were also taken from normal control subjects. Mast cells and solar elastosis areas were evaluated using a computer-assisted image-analysis program. Lesional skin had abundant elastotic material compared with nonaffected skin (13.3 ± 2.8% vs. 10.2 ± 2.9%, P < 0.001). Mast cells were more prominent in the elastotic areas of melasma skin (173 ± 57% vs. 145 ± 57%, P = 0.04). Melasma could be a result of a cumulative sun exposure, in a microenvironment of cutaneous photoageing in which inflammatory cells, particularly mast cells, play a key role.

Periodontal disease involves inflammation of the gingival tissues, caused by microbial pathogens. Recent papers suggest that emotional stress worsens periodontal disease. Here we review the literature and propose that corticotropin-releasing hormone (CRH) secreted under stress stimulates gingival mast cells together with other neuropeptides and cytokines to secrete pro-inflammatory molecules that contribute to periodontal pathology. Stress reduction and/or mast cell inhibition may provide additional therapeutic approaches.

We report a rapid method for the direct multicolor imaging of multiple subnuclear genetic sequences using novel quantum dot-based fluorescence in situ hybridization (FISH) probes (QD-FISH). Short DNA oligonucleotides were attached on QDs and used in a single hybridization/ detection step of target sites in situ. QD-FISH probes penetrate both intact interphase nuclei and metaphase chromosomes and showed good targeting of dense chromatin domains with minimal steric hindrances. We further demonstrated that QD's broad absorption spectra allowed different colored probes specific for distinct subnuclear genetic sequences to be simultaneously excited with a single excitation wavelength and imaged free of chromatic aberrations in a single exposure. Thus, these results demonstrate that QD-FISH probes are very effective in multicolor FISH applications. This work also documents new possibilities of using QD-FISH probes detection down to the single molecule level. NOTE ADDED IN PROOF As this manuscript went to press, Chan et al. published a similar QD-FISH method for the multiplex detection of mRNAs (24). Recent results by Xiao et al. suggest that pH effects on fluorescence of QD-detected hybridization signals could account for the absence of QD centromeric hybridization signals on human metaphase chromosomes in their FISH experiments (25).

Previous in vitro studies have demonstrated that mast cells (MC) can be directly activated by Trichinella spiralis larvae 1 (TSL-1) antigens. To characterize even more this activation of MC and their possible role on induction and regulation of the Type 2 response generated against T. spiralis infection, we studied the interaction between a hybrid rat MC line (HRMC), murine bone marrow MC (mBMMC), and TSL-1 antigens. Immunofluorescence staining and flow cytometry analysis showed that TSL-1 antigens bound to the surface of HRMC cells, resulting in the transcriptional induction and in the release of TNF and IL-4. Besides, an increase of IL-4 intracellular expression was also observed in mBMMC. This suggests that MC may play an important role in the early immune response against T. spiralis and may be a source of cytokines, that regulate the final onset of the immune mechanisms which determine the course of the infection.

It is well established that human mast cell proliferation and maturation are regulated by kit ligand (stem cell factor). Little is known, however, about how these two processes are negatively regulated and thus, how mast cell number is controlled in normal and pathologic conditions. We therefore first hypothesized that SCF-dependent human mast cells would undergo programmed cell death (apoptosis) on removal of SCF as has been shown for growth factor-dependent rodent mast cells. We then examined whether SCF acts as a survival factor through the regulation of the bcl-2 family of apoptosis-regulatory genes. As hypothesized, elimination of SCF from primary peripheral blood-derived human mast cell cultures resulted in a significant apoptotic process. During apoptosis, down-regulation of the two apoptosis-regulatory proteins Bcl-2 and Bcl-XL was observed. Moreover, a deregulated expression of these two proteins was found in two human mast cell lines which are SCF-independent. Thus, SCF fu...

Los trastornos funcionales digestivos y el síndrome de intestino irritable, en particular, constituyen una de las causas más habituales de consulta médica y el diagnóstico más frecuente realizado por el especialista de aparato digestivo. A pesar de su elevada prevalencia, la etiología y fisiopatología de los procesos funcionales digestivos no están bien establecidas, y tampoco hay métodos diagnósticos específicos ni opciones terapéuticas claramente eficaces. Por todo ello, estos pacientes experimentan a menudo un deterioro importante de su calidad de vida que condiciona un gasto sanitario creciente. Evidencias recientes indican que la presencia de microinflamación en la mucosa intestinal con hiperplasia mastocitaria podría contribuir al desarrollo y perpetuación de los patrones de hipersensibilidad visceral, dismotilidad y alteraciones de la barrera epitelial que caracterizan al síndrome de intestino irritable. En este artículo revisaremos el papel del eje estrés-mastocito en la modulación de la inflamación de la mucosa intestinal y en la patogenia del síndrome de intestino irritable.

The skin, the body's largest organ, helps to secure the integrity of the host and, at the same time, allows the individual to communicate with the outside world. This finely tuned balance between protection from harmful pathogens (mostly microorganisms) and bidirectional signal exchange is provided by a network of structural, cellular, and molecular elements that are collectively referred to as the skin barrier. This "gateway" has a physical, chemical, and immunologic component. The role of the latter is to elicit a powerful defense reaction in the case of danger and, at the same time, to prevent such a reaction against innocuous substances. Immune responses originating in the skin are mounted and executed by cells and molecules of the innate or the adaptive immune system. Innate reactions are typically rapid, poorly discriminating, and do not exhibit memory. Adaptive responses, in contrast, show a high degree of specificity as well as memory but need a protracted time for their development. As a consequence, innate and adaptive responses are consecutive events influencing each other. In fact, we now know that the type and magnitude of the innate reactions govern and often determine the quality and quantity of adaptive responses.

Epidemiological studies have suggested inverse associations between allergic diseases and malignancies. As a proof of concept for the capability of immunoglobulin E (IgE) to destruct tumor cells, several experimental strategies have evolved to specifically target this antibody class towards relevant tumor antigens. It could be demonstrated that IgE antibodies specific to overexpressed tumor antigens have been superior to any other immunoglobulin class with respect to antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) reactions. In an alternative approach, IgE nonspecifically attached to tumor cells proved to be a powerful adjuvant establishing tumor-specific immune memory. Active Th2 immunity could also be achieved by applying an oral immunization regimen using mimotopes, i.e. epitope mimics of tumor antigens. The induced IgE antibodies could be cross-linked by live tumor cells leading to tumoricidic mediator release. Thus, IgE antibodies may not only act in natural tumor surveillance, but could possibly also be exploited for tumor control in active and passive immunotherapy settings. Thereby, eosinophils, mast cells and macrophages can be armed with the cytophilic IgE and become potent anti-tumor effectors, able to trace viable tumor cells in the tissues. It is strongly suggested that the evolving new field AllergoOncology will give new insights into the role of IgEmediated allergy in malignancies, possibly opening new avenues for tumor therapy.

Risk assessment of individuals with anaphylaxis is currently hampered by lack of (1) an optimal and readily available laboratory test to confirm the clinical diagnosis of an anaphylaxis episode and (2) an optimal method of distinguishing allergensensitized individuals who are clinically tolerant from those at risk for anaphylaxis episodes after exposure to the relevant allergen. Our objectives were to review the effector mechanisms involved in the pathophysiology of anaphylaxis; to explore the possibility of developing an optimal laboratory test to confirm the diagnosis of an anaphylaxis episode, and the possibility of improving methods to distinguish allergen sensitization from clinical reactivity; and to develop a research agenda for risk assessment in anaphylaxis. Researchers from the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergology and Clinical Immunology held a PRACTALL (Practical Allergy) meeting to discuss these objectives. New approaches being investigated to support the clinical diagnosis of anaphylaxis include serial measurements of total tryptase in serum during an anaphylaxis episode, and measurement of baseline total tryptase levels after the episode. Greater availability of the test for mature b-tryptase, a more specific mast cell activation marker for anaphylaxis than total tryptase, is needed. Measurement of chymase, mast cell carboxypeptidase A3, platelet-activating factor, and other mast cell products may prove to be useful. Consideration should be given to measuring a panel of mediators from mast cells and basophils. New approaches being investigated to help distinguish sensitized individuals at minimum or no risk from those at increased risk of developing anaphylaxis include measurement of the ratio of allergen-specific IgE to total IgE, determination of IgE directed at specific allergenic epitopes, measurement of basophil activation markers by using flow cytometry, and assessment of allergen-specific cytokine responses. Algorithms have been developed for risk assessment of individuals with anaphylaxis, along with a research agenda for studies that could lead to an improved ability to confirm the clinical diagnosis of anaphylaxis and to identify allergensensitized individuals who are at increased risk of anaphylaxis. (J Allergy Clin Immunol 2007;120: S2-24.)

We examined whether neuronal proteinase-activated receptor-2 (PAR-2) may be involved in pruritus of human skin. The endogenous PAR-2 agonist tryptase was increased up to fourfold in atopic dermatitis (AD) patients. PAR-2 was markedly enhanced on primary afferent nerve fibers in skin biopsies of AD patients. Intracutaneous injection of endogenous PAR-2 agonists provoked enhanced and prolonged itch when applied intralesionally. Moreover, itch upon mast cell degranulation was abolished by local antihistamines in controls but prevailed in AD patients. Thus, we identified enhanced PAR-2 signaling as a new link between inflammatory and sensory phenomena in AD patients. PAR-2 therefore represents a promising therapeutic target for the treatment of cutaneous neurogenic inflammation and pruritus.

To better understand the therapeutic effectiveness of acupuncture, questions about the underlying mechanisms need to be addressed. Here we describe the impact of manual stimulation by an acupuncture needle of zusanli (stomach 36 [ST36]) on analgesia in rats. The analgesic effect was more pronounced after stimulation of ST36 than after stimulation of a sham point near the acupuncture point. At the same time, we determined in tissue slices the density of mast cells in the acupuncture points and nearby points, as well as the degree of degranulation before and after stimulation. We found that the density of mast cells from the ST36 of rats was higher than that from a nearby sham point. In addition, acupuncture resulted in a remarkable increase in degranulation of the mast cells. Pretreatment of the acupuncture point with disodium chromoglycate not only counteracted the phenomenon of degranulation but also reduced analgesic effect of acupuncture. Our experiments on inhibition of degranulation of mast cells in tissue from acupuncture points demonstrates the possible role of mast cells in acupuncture effects.

Mast cells are best known for their potent effector functions in allergic disorders. In recent years, however, mast cells have been identified to be involved in a surprisingly complex range of immune functions that go far beyond allergies and include the development of autoimmune disorders and peripheral tolerance, and the initiation and maintenance of adaptive and innate host responses. Here, we review the key signals and effector mechanisms that have lately been identified for mast cell functions in these immune responses.

Immunoglobulin (Ig) E-dependent activation of mast cells is central to the allergic response. The engagement of IgE-occupied receptors initiates a series of molecular events that causes the release of preformed, and de novo synthesis of, allergic mediators. Cysteinyl leukotrienes are able to contract airway smooth muscle and increase mucus secretion and vascular permeability and recruit eosinophils. Mast cells have also

Urinary excretion of previously identi ed mediators of EIB was investigated in association with mannitol-induced bronchoconstriction. Twelve asthmatic and nine nonasthmatic subjects inhaled mannitol and urine was collected 60 min before and for 90 min after challenge. The urinary concentrations of leukotriene (LT)E 4 , the prostaglandin (PG)D 2 metabolite and the mast cell marker 9a,11b-PGF 2 were measured by enzyme immunoassay. N t -methylhistamine was measured by radioimmunoassay.