Mast cell activation syndrome:An up-to-date review of literature

Mast cells are a subtype of white blood cells and are involved in the immune system.These cells contain many chemical substances called mediators,which are involved in the allergic response.The fact that mast cells play a role in many events that require urgent intervention,especially anaphylaxis,has led to a more detailed study of these cells.The diseases also caused by dysfunctions of mast cells have been examined in many circumstances.For instance,mast cell activation syndrome is known as an augmented number of cells due to decreased cell death,resulting in clinical symptoms affecting many systems.The main common symptoms include flushing,hypotension,urticaria,angioedema,headache,vomiting and diarrhea.Although the underlying mechanism is not yet clearly known,we aim to review the literature in a broad perspective and bring together the existing knowledge in the light of the literature due to the diversity of its involvement in the body and the fact that it is a little known syndrome.

Treatment refractory mast cell leukemia with dominant gastrointestinal manifestation and concomitant skin symptoms:A case report

BACKGROUND Mast cell leukemia(MCL),a subtype of systemic mastocytosis(SM),is an extremely rare clinical entity characterized by a very poor prognosis.Chemotherapy,tyrosine kinase inhibitors,and allogeneic hematopoietic cell transplantation are the only treatment options,but they cannot provide the desired outcomes in most cases of MCL.However,other types of SM can be successfully treated.The disease has no specific manifestation,but gastroenterological symptoms are present in most cases.CASE SUMMARY The authors,hereby,report a case of a 46-year-old female patient diagnosed with MCL-the rarest subtype of SM.The patient presented to the gastroenterology clinic with multiple,various,and unspecific gastroenterological symptoms.Concomitance of skin lesions significantly contributed to a relatively prompt diagnosis.The serum tryptase level was extremely high and bone the marrow aspirate showed an infiltration of atypical mast cells.The disease was rapidly progressive and primary refractory to chemotherapy and the patient succumbed to the illness about a month after the initiation of treatment.CONCLUSION Despite its“hematological nature”,MCL,in most cases presents dominantly with unspecific gastroenterological symptoms.Thus,a high disease awareness among physicians other than hematologists is necessary to improve treatment outcomes.Serum tryptase level,due to its non-invasive nature and easy access,may serve as an initial step to estimate the probability of mastocytosis.

Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis by inhibiting mast cell degranulation

Background:In this study,we investigated whether prophylactic treatment with Guizhi-Shaoyao-Zhimu decoction(GSZ)could delay the onset of rheumatoid arthritis by targeting mast cells.Methods:Collagen-induced arthritis was used to evaluate the effect of GSZ in preventing arthritis and joint destruction.Immunohistochemical staining revealed the accumulation of histamine H4 receptor and tryptase alpha/beta-1 in the ankle joint of the model.Then,we explored the effect of GSZ serum on fibroblast-like synoviocytes using standard transwell invasion and migration assays.Real-time quantitative polymerase chain reaction and western blot were used to detect the expression of toll-like receptor 4(TLR4)/myeloid differentiationfactor 88(MyD88)/nuclear factor-κB p65(NF-κB p65).Results:The results showed that pre-rheumatoid arthritis treatment with GSZ could reduce inflammation and maintain cartilage structure in the collagen-induced arthritis model.Moreover,GSZ significantly blocked mast cell degranulation and inhibited the TLR4/MyD88/NF-κB p65 pathway.Since the combined activation of mast cells via TLR4 and immune complexes enhances inflammation in synovial tissue,we concluded that GSZ may block mast cell degranulation by inhibiting the TLR4/MyD88/NF-κB p65 pathway and thus influence rheumatoid arthritis onset.Conclusion:Taken together,our data suggested that GSZ may be a promising therapeutic decoction for the prophylactic treatment of rheumatoid arthritis.

HISTOCHEMICAL TECHNIQUES IDENTIFYING MAST CELLS IN PIG,CATTLE AND SHEEP

Carnoy′s fluid and neutral buffered formalin(NBF)have been proved to be good fixatives for preservation of mast cells in pig,cattle and sheep except NBF blocked staining of most porcine mast cells,especially those located in intestinal mucosa(MMC)and in thymus medulla(TMMC). Both toluidine blue and Alcian blue were the excellent stains generally,but Alcian blue stained more porcine mast cells than did toluidine blue( P <0 01). Staining with toluidine blue of a wide pH range(from 0 1 to 7 0)showed that porcine mast cells were not very pH dependent,but the dye at pH 0 5 seemed to have the strongest affinity for all mast cells in pigs and it was also suitable for bovine and ovine mast cell staining. In the three species,unlike in rodents,the Alcian blue method did not distinguish between mast cells in the intestinal mucosa(MMC)and those in the connective tissue of the intestinal submucosa,tongue and skin(CTMC). Porcine CTMC,but not MMC,fluoresced strongly when stained with berberine sulphate or with a mixture of berberine sulphate and acridine orange. It suggested that porcine CTMC contained heparin proteoglycan.

Effect of fexofenadine, a mast cell blocker, in infertile men with significantly increased testicular mast cells

Aim: To investigate the role of fexofenadine, a mast cell blocker, on semen quality in the treatment of infertile men. Methods: The study included 16 Turkish idiopathic infertile men with azoospermia or oligozoospermia who underwent testicular biopsy to examine mast cells containing tryptase. In all patients, a complete medical history, clinical examination, semen analysis and serum hormone assay were carried out. The biopsy specimens were immunohistochemically stained with antihuman tryptase for mast cells. The number of total mast cells per seminiferous tubule was calculated and recorded as mast cell index. The patients were divided into two groups according to their mast cell index: the higher (≥1, n=9) and the lower (<1, n=7) index groups. Fexofenadine was administered orally at a dose of 180 mg/day for 4 to 9 months. Pre-and post-treatment semen parameters, including total motile sperm counts (TMC) were recorded and compared. Spontaneous pregnancies after the treatment were registered. Results: There was no statistically significant difference in TMC between the pre-treatment and post-treatment values in patients with higher and lower mast cell index (P≥0.05). In both groups, nobody had a significant response to the treatment and there was no spontaneous pregnancy after the treatment. Conclusion: Although testicular dysfunction is closely associated with increased number of testicular mast cells, fexofenadine, a mast cell blocker, appears not having any benefit in the treatment of Turkish infertile men with a significant increase in testicular mast cells. (Asian J Androl 2002 Dec; 4: 291-294)

Effects of fluoxetine on mast cell morphology and protease-1 expression in gastric antrum in a rat model of depression

AIM: To investigate the effects of fluoxetine on depression-induced changes of mast cell morphology and protease-1 (rMCP-1) expression in rats. METHODS: A Sprague-Dawley rat model of chronic stress-induced depression was established. Fifty experimental rats were randomly divided into the following groups: normal control group, fluoxetine + normal control group, depressed model group, saline + depressed model group, and fluoxetine + depressed model group. Laser scanning confocal microscopy (LSCM) immunofluorecence and RT-PCR techniques were used to investigate rMCP-1 expression in gastric antrum. Mast cell morphology was observed under transmission electron microscopy. ANOVA was used for statistical analysis among groups.RESULTS: Morphologic observation indicated that depression induced mast cell proliferation, activation, and granule hyperplasia. Compared with the normal control group, the average immunofluorescence intensity of gastric antrum rMCP-1 significantly increased in depressed model group (37.4 ± 7.7 vs 24.5 ± 5.6, P < 0.01) or saline + depressed model group (39.9 ± 5.0 vs 24.5 ± 5.6, P < 0.01), while there was no significant difference between fluoxetine + normal control group (23.1 ± 3.4) or fluoxetine + depressed model group (26.1 ± 3.6) and normal control group.The average level of rMCP-1mRNA of gastric antrum significantly increased in depressed model group (0.759 ± 0.357 vs 0.476 ± 0.029, P < 0.01) or saline + depressed model group (0.781 ± 0.451 vs 0.476 ± 0.029, P < 0.01 ), while no significant difference was found between fluoxetine + normal control group (0.460 ± 0.027) or fluoxetine + depressed model group (0.488 ± 0.030) and normal control group. Fluoxetine showed partial inhibitive effects on mast cell ultrastructural alterations and de-regulated rMCP-1 expression in gastric antrum of the depressed rat model.CONCLUSION: Chronic stress can induce mast cell proliferation, activation, and granule hyperplasia in gastric antrum. Fluoxetine counteracts such changes in the depressed rat model.

Effects of N-(3',4',5'-Trimethoxycinnamoyl) ortho-Aminobenzoic Acid on Antigen-induced Contraction of Guinea-pig Ileum and the Degranulation of and Histamine Release from Mast Cells

N-(3′,4′,5′-Trimethoxycinnamoyl)ortho-aminobenzoic acid(TOA),at the concentration of 80μg/ml,significantly inhibited the antigen-induced contraction of ileum isolated from the actively sensitized guinea-pig.At the concentrations of 25 and 50μg/ml, TOA inhibited homocytotropic antibody-mediated degranulation of mast cells in the rat mesentery,and also inhibited anaphylactic histamine release from rat peritoneal mast cells.

Mast cell activation syndrome-anesthetic challenges in two different clinical scenarios

Mast cell activation syndrome(MCAS)includes a group of disorders that result in the inappropriate release of inflammatory mediators from mast cells.These mediators can affect multiple organ systems and lead to significant morbidity,and possible fatality.Although reactions,typically in response to various nonspecific stimuli,are usually mild,they may put those with MCAS at increased risk of anaphylaxis.In this case report,we present two clinical scenarios of MCAS,and identify possible factors triggering mast cell mediator release.We also define a preoperative preventive pathway,outline anesthetic considerations,and discuss the management of immediate hypersensitivity reactions in patients with MCAS.Meticulous preoperative preparation,avoidance of triggers,and development of a plan to treat possible adverse organ responses are paramount of good outcomes.

Mast Cells:The Key to Multiple Sclerosis?

Mast cells are present in high numbers in the border-zones of the multiple sclerosis-plaques. They are located in small clusters along capillaries and venules, and they are more abundant in females than in men. Mast cells can be stimulated to release specific mediators such as histamine, resulting in oedema formation, as well as proteases that may cause demyelination, by several different activation mechanisms. We hypothesize that a putative mast cell activation may be induced by diet factor(s) as well as long lasting mental stress that may lead to the release of catestatin, as well as ACTH released from the pituitary gland. Given a natural flux of mast cell recovery and activation, a putative phenomenon of massive release of mediators and “silent” reload periods may explain the relapsing-remitting phases of multiple sclerosis.

Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome

AIM: To investigate if there are changes in serotonin (5-HT) levels, enterochromaffin (EC) cells and mast cells in small intestinal mucosa of patients with irritable bowel syndrome (IBS). METHODS: Diarrhea-predominant (IBS-D, n = 20), or constipation-predominant (IBS-C, n = 18) IBS patients and healthy controls (n = 20) underwent colonoscopy and peroral small intestinal endoscopy, and mucosal samples were obtained at the descending part of the duodenum, proximal end of jejunum and terminal ileum. High-performance liquid chromatography- electrochemistry and immunohistochemical methods were used to detect 5-HT content, EC cells and mast cells. RESULTS: (1) There were no differences in the number and distribution of EC cells between IBS patients and the normal group. (2) The mucosal 5-HT contents at the duodenum, jejunum and ileum in IBS-C patients were 182 ± 90, 122 ± 54, 61 ± 35 ng/mg protein, respectively, which were all lower than those in the normal group (256 ± 84, 188 ± 91, and 93 ± 45 ng/ mg protein, respectively), with a significant difference at the jejunum (P < 0.05). There were no differences in the small intestinal mucosal 5-HT contents between IBS-D patients and the normal group. The mucosal 5-HT contents at the duodenum were significantly higher than those at the ileum in the three groups (P < 0.001). (3) The numbers of mast cells in patients with IBS-C and IBS-D at the ileum were 38.7 ± 9.4 and 35.8 ± 5.5/highpower field (hpf), respectively, which were significantly more than that in the normal group (29.8 ± 4.4/hpf) (P < 0.001). There was no significant difference in the numbers of mast cells at the other two parts between IBS patients and the normal group. The numbers of mast cells in IBS-C, IBS-D, and normal groups were all significantly higher at the ileum (38.7 ± 9.4, 35.8 ± 5.5, 29.8 ± 4.4/hpf, respectively) than at the duodenum (19.6 ± 4.7, 18.5 ± 6.3, 19.2 ± 3.3/hpf, respectively, P < 0.001). CONCLUSION: The changes in the 5-HT signaling pathway at the jejunum of IBS-C patients and the increase in mast cells in patients with IBS at the terminal ileum may offer evidence to explain the pathogenesis of IBS.

Pancreatic and pulmonary mast cells activation during experimental acute pancreatitis

AIM:To study the activation of pancreatic and pulmonary mast cells and the effect of mast cell inhibition on the activation of peritoneal and alveolar macrophages during acute pancreatitis.METHODS:Pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate in rats.The mast cell inhibitor cromolyn was administered intraperitoneally(i.p.) 30 min before pancreatitis induction.The pancreatic and pulmonary tissue damage was evaluated histologically and mast cells and their state of activation were evaluated.Peritoneal and alveolar macrophages were obtained and the expression of tumor necrosis factor α was determined.Myeloperoxidase activity was measured to evaluate the effect of mast cell inhibition on the progression of the inflammatory process.Finally,the effect of plasma on cultured mast cells or macrophages was evaluated in vitro.RESULTS:The mast cell stabilizer signif icantly reduced inflammation in the pancreas and lung and the activation of alveolar macrophages but had no effect on peritoneal macrophages.Mast cell degranulation was observed in the pancreas during pancreatitis but no changes were observed in the lung.Plasma from rats with pancreatitis could activate alveolar macrophages but did not induce degranulation of mast cells in vitro.CONCLUSION:Pancreatic mast cells play an important role in triggering the local and systemic inflammatory response in the early stages of acute pancreatitis.In contrast,lung mast cells are not directly involved in the inflammatory response related to pancreatic damage.

Alterations of mast cells and TGF-β1 on the silymarin treatment for CCl_4-induced hepatic fibrosis

AIM: Silymarin is a potent antioxidant, antiinflammatory and anti-fibrogenic agent in the liver, which is mediated by alteration of hepatic Kupffer cell function, lipid peroxidation, and collagen production. Especially, in hepatic fibrogenesis, mast cells are expressed in chronic inflammatory conditions, and promote fibroblast growth and stimulate production of the extracellular matrix by hepatic stellate cells. METHODS: We examined the inhibitory mechanism of silymarin on CCI4-induced hepatic cirrhosis in rats. At 4, 8, and 12 wk, liver tissues were examined histopathologically for fibrotic changes produced by silymarin treatment. RESULTS: In the silymarin with CCU-treated group, increase of hepatic stellate cells and TGF-β1 production were lower than in the CCI4-treated group at early stages. Additionally, at the late fibrogenic stage, expressions of TGF-β1 were weaker and especially not expressed in hepatocytes located in peripheral areas. Moreover, the number of mast cell in portal areas gradually increased and was dependent on the fibrogenic stage, but those of CCI4+silymarin-treated group decreased significantly. CONCLUSION: Anti-fibrotic and antiinflammatory effects of silymarin were associated with activation of hepatic stellate cells through the expression of TGF-β1 and stabilization of mast cells. These results suggest that silymarin prevent hepatic fibrosis through suppression of inflammation and hypoxia in the hepatic fibrogenesis.

Mucosal mast cells are pivotal elements in inflammatory bowel disease that connect the dots:Stress,intestinal hyperpermeability and inflammation

Mast cells (MC) are pivotal elements in several physiological and immunological functions of the gastro- intestinal (GI) tract. MC translate the stress signals that has been transmitted through brain gut axis into release of proinflammatory mediators that can cause stimulation of nerve endings that could affect afferent nerve terminals and change their perception, affect intestinal motility, increase intestinal hyperpermeability and, in susceptible individuals, modulate the inflammation. Thus, it is not surprising that MC are an important element in the pathogenesis of inflammatory bowel disease and non inflammatory GI disorders such as IBS and mast cell enterocolitis.

Mast cell density and the context of clinicopathological parameters and expression of p185,estrogen receptor,and proliferating cell nuclear antigen in gastric carcinoma

AIM:To investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p185,estrogen receptor(ER), and proliferating cell nuclear antigen(PCNA)in gastric carcinoma. METHODS:Mast cell,p185,ER,and PCNA were detected using immunohistochemical S-P labeling method.Mast cell was counted in tissue of gastric carcinoma and regional lymph nodes respectively,and involved lymph nodes(ILN)were examined as usual. RESULTS:MCD was significantly related to both age and depth of penetration(x^2=4.688,P<0.05 for age and x^2=9.350, P<0.01 for depth of penetration)between MCD>21/0.03 mm^2 and MCD≤21/0.03 mm^2 in 100 patients;MCD in 1-6 ILN group patients was significantly higher than that in 7-15 ILN or>15 ILN group patients(u=6.881,8.055,P<0.01); There were significant differences intergroup in positive expression rate of p185,ER and PCNA between MCD>21/ 0.03 mm^2 and MCD≤21/0.03 mm^2 in 100 patients. CONCLUSION:Mast cell may have effect on inhibiting invasive growth of tumor,especially in the aged patients; The number of mast cells,in certain degree,may predicate the number of involved lymph nodes,which is valuable for assessment of prognosis;MCD was related to the expression of p185,ER,and PCNA in gastric carcinoma.It suggests that mast cell accumulation may inhibit the proliferation and the dissemination of the gastric carcinoma. INTRODUCTION Recently,many studies have reported on the association of mast cell with various tumorst.In several malignancies,mast cell has been found to correlate with growth,penetration and prognosis of tumor.Therefore,our study was undertaken to investigate the relationship between the mast cell density (MCD)and the context of clinicopathological parameters and expression of p 185,estrogen receptor(ER),and proliferating cell nuclear antigen(PCNA)in gastric carcinoma.

Role of mast cell-mi R-490-5p in irritable bowel syndrome

AIM To determine the functional role of mi R-490-5p in mast cell proliferation and apoptosis,and in the mast cell tryptase/PAR-2 signal pathway.METHODS The 3rd generation of lentivirus vector systems containing enhanced green fluorescent protein(EGFP)(Ruisai Inc.,Shanghai,China),which acts as a reporter gene was used to construct the mmu-mi R-490-5p lentivirus expression vector p EGFP-antagomi R-490-5p,and the lentivirus vector p EGFP-negative was used as a negative control.The stably transfected mast cell line p815 was then constructed.GFP positive cells were successfully transfected cells.We determined the expression of mi R-490-5p in p815 mast cells before and after transfection using quantitative real-time PCR(q RT-PCR).In addition,after transduction with the lentivirus vectors,the role of mi R-490-5p in mast cell proliferation and apoptosis was investigated using the CCK-8 assay and flow cytometry,respectively.The m RNA levels of tryptase and PAR-2 were detected by q RT-PCR and the protein levels were detected by Western blot.RESULTS The inhibition of mi R-490-5p expression promoted apoptosis and inhibited proliferation of p815 mast cells.The m RNA levels of tryptase and PAR-2 were significantly increased after transfection comparedwith the control group,tryptase(P=0.721,normal vs null;P=0.001,si RNA vs normal;P=0.002,si RNA vs null)and PAR-2(P=0.027,si RNA vs null;P=0.353,normal vs null;P=0.105,si RNA vs normal).The protein levels of tryptase and PAR2 were slightly higher in the si RNA group than those in the control group,but the difference was not statistically significant(P>0.05).CONCLUSION mi R-490-5p plays a vital role in the pathogenesis of irritable bowel syndrome by affecting mast cell proliferation and apoptosis;with down-regulation of mi R-490-5p,the m RNA level of mast cell tryptase and PAR-2 increased,and the protein level increased,but the difference was not statistically significant.

Possible biological and translational significance of mast cells density in colorectal cancer

Mast cells (MCs), located ubiquitously near blood vessels, are descended from CD34+ hematopoietic stem cells. Initially, although their role has been well defined in hypersensitivity reactions, the discovery of their sharing in both innate and adaptive immunity has allowed to redefine their crucial interplay on the regulatory function between inflammatory and tumor cells through the release of mediators granule-associated (mainly tryptase and vascular endothelial growth factor). In particular, in several animal and human malignancies it has been well demonstrated that activated c-Kit receptor (c-KitR) and tryptase (an agonist of the proteinase-activated receptor-2) take pivotal part in tumor angiogenesis after the MCs activation, contributing to tumor cells invasion and metastasis. In this review, we focused on crucial MCs density (MCD) role in colorectal cancer (CRC) development and progression angiogenesis-mediated; then, we will analyze the principal studies that have focused on MCD as possible prognostic factor. Finally, we will consider a possible role of MCD as novel therapeutic target mainly by c-KitR tyrosine kinase inhibitors (imatinib, masitinib) and tryptase inhibitors (gabexate and nafamostat mesylate) with the aim to prevent CRC progression.

Moxibustion activates mast cell degranulation at the ST25 in rats with colitis

AIM: To investigate the effects of moxibustion on the morphology and function of mast cells (MC) at Tianshu (ST25) in rats with trinitro-benzene-sulfonic acid (TNBS)-induced colitis. METHODS: A total of 53 male Sprague-Dawley rats were randomly divided into a normal group and experimental group. In the experimental group, a rat model of TNBS-induced colitis was established, and the rats were then randomly divided into a model group, moxi-bustion group, moxibustion plus disodium cromoglycate (M + DC) group and moxibustion plus normal saline (M+ NS) group. Rats in the moxibustion group received suspended moxibustion at bilateral ST25 for 10 min, once a day for 7 d. Rats in the M + DC and M + NS groups were pretreated with disodium cromoglycate and normal saline at bilateral ST25, respectively, and were then concurrently subjected to the same treatment as rats in the moxibustion group. The hematoxy- lin-eosin staining method was used to observe histology of the colon and the toluidine blue-improved method was used to observe mast cells at ST25 acupoint areas. RESULTS: An improvement in colonic injury in the moxibustion group was observed and the degranulation ratio of MC at ST25 acupoint was markedly higher in the moxibustion group than in the model group (45.91 ± 11.41 vs 32.58 ± 8.28, P < 0.05). After inhibition of degranulation of MC at ST25 by disodium cromoglycate, no improvement in colon tissue injury was observed. CONCLUSION: Moxibustion exerted its effect on healing impaired colonic mucosa in rats with TNBS-induced colitis by increasing the degranulation ratio of local MC, but had little effect on the morphology of MC at ST25 acupoint.

Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cells

AIM:To investigate the effects of four probiotic bacteria and their combination on human mast cell gene expression using microarray analysis.METHODS:Human peripheral-blood-derived mast cells were stimulated with Lactobacillus rhamnosus (L.rhamnosus) GG (LGG),L.rhamnosus Lc705 (Lc705),Propionibacterium freudenreichii ssp.shermanii JS (PJS) and Bifidobacterium animalis ssp.lactis Bb12 (Bb12) and their combination for 3 or 24 h,and were subjected to global microarray analysis using an Affymetrix GeneChip Human Genome U133 Plus 2.0 Array.The gene expression differences between unstimulated and bacteria-stimulated samples were further analyzed with GOrilla Gene Enrichment Analysis and Visualization Tool and MeV Multiexperiment Viewer-tool.RESULTS:LGG and Lc705 were observed to suppress genes that encoded allergy-related high-affinity IgE receptor subunits α and γ (FCER1A and FCER1G,respectively) and histamine H4 receptor.LGG,Lc705 and the combination of four probiotics had the strongest effect on the expression of genes involved in mast cell immune system regulation,and on several genes that encoded proteins with a pro-inflammatory impact,such as interleukin (IL)-8 and tumour necrosis factor alpha.Also genes that encoded proteins with anti-inflammatory functions,such as IL-10,were upregulated.CONCLUSION:Certain probiotic bacteria might diminish mast cell allergy-related activation by downregulation of the expression of high-affinity IgE and histamine receptor genes,and by inducing a pro-inflammatory response.

Roles and relevance of mast cells in infection and vaccination

In addition to their well-established role in allergy mast cells have been described as contributing to functional regulation of both innate and adaptive immune responses in host defense. Mast cells are of hematopoietic origin but typically complete their differentiation in tissues where they express immune regulatory functions by releasing diverse mediators and cytokines. Mast cells are abundant at mucosal tissues which are portals of entry for common infectious agents in addition to allergens. Here, we review the current understanding of the participation of mast cells in defense against infection. We also discuss possibilities of exploiting mast cell activation to provide adequate adjuvant activity that is needed in high-quality vaccination against infectious diseases.

Immunosurveillance function of human mast cell?

Mast cell (MC) is so widely recognized as a critical effector in allergic disorders that it can be difficult to think of MC in any other context. Indeed, MCs are multifunctional and recently shown that MCs can also act as antigen presenters as well as effector elements of human immune system. First observations of their possible role as anti-tumor cells in peri- or intra-tumoral tissue were mentioned five decades ago and a high content of MCs is considered as a favorable prognosis,consistent with this study. Believers of this hypothesis assumed them to be inhibitors of tumor development through their pro-apoptotic and -necrolytic granules e.g.,granzymes and TNF-α. However, some still postulate them to be enhancers of tumor development through their effects on angiogenesis due to mostly tryptase.There are also some data suggesting increased MC density causes tumor development and indicates bad prognosis. Furthermore, since MC-associated mediators have shown to influence various aspects of tumor biology, the net effect of MCs on the development/progression of tumors has been difficult to evaluate. For instance, chymase induces apoptosis in targets; yet,tryptase, another MC protease, is a well-known mitogen.MCs with these various enzyme expression patterns may mediate different functions and the predominant MC type in tissues may be determined by the environmental needs. The coexistence of tryptase-expressing MCs(MCT) and chymase and tryptase-expressing MCs (MCTC)in physiological conditions reflects a naturally occurring balance that contributes to tissue homeostasis. We have recently discussed the role and relevance of MC serine proteases in different bone marrow diseases.