Mast cells in cystadenolymphomas

Summary Cystadenolymphomas are a special kind of salivary gland tumours with an epithelial and a stromal part. Mast cells, which in this tumour were only rarely mentioned, were observed in large amounts in the stroma and in the epithelium. This type of cell is present especially in those cystadenolymphomas rich in epithelial parts. The possible significance of this observation is discussed.Supported by the Deutsche Forschungsgemeinschaft and by the Hamburger Stiftung zur Förderung der Krebsbekämpfung     

Endothelial cell changes in acute hepatitis. A light and electron microscopic study

Hepatic endothelial cells were studied by light and electron microscopy in 48 patients with acute hepatitis due to virus infection or drug idiosyncrasy. Light microscopy revealed cell swelling and appearance of dense refractile intracytoplasmic granules staining with the amylase PAS reaction and for iron by Perls' method. They were orcein-negative. These cells, regarded as 'activated' endothelial cells, were found throughout the parenchyma, especially in the classical form of acute hepatitis. In acute hepatitis with bridging, panacinar or periportal necrosis, activated endothelial cells were prominent in the necrotic areas. They were constantly seen lining newly formed capillaries in these sites. By electron microscopy, the intracytoplasmic granules had the characteristics of primary or secondary siderosomes. In areas of capillarization, basement membrane material was seen on the aspect of the activated cells facing the space of Disse. Activated endothelial cells may play a part in protecting hepatocytes from injury.     

Mast cells and angiogenesis

Angiogenesis is tightly regulated by pro- and anti-angiogenic factors. Secreting mast cells are able to induce and enhance angiogenesis via multiple in part interacting pathways. They include mast cell-derived (i) potent pro-angiogenic factors such as VEGF, bFGF, TGF-beta, TNF-alpha and IL-8, (ii) proteinases and heparin, that release heparin-binding pro-angiogenic factors lodged on cell surfaces and in the extracellular matrix (ECM), (iii) histamine, VEGF, and certain lipid-derived mediators that induce microvascular hyperpermeability having pro-angiogenic effects, (iv) chemotactic recruitment of monocytes/macrophages and lymphocytes that are able to contribute with angiogenesis-modulating molecules, (v) activation of platelets that release pro-angiogenic factors, (vi) activation of neighboring stationary non-mast cells, which secrete pro-angiogenic factors, ECM-degrading proteinases and stem cell factor which attracts, mitogenically stimulates and activates mast cells, (vii) auto- and paracrine stimulation of mast cells by stem cell factor, (viii) recruitment of mast cells by pro-angiogenic factors such as VEGF, bFGF and TGF-beta. As a result of ECM-degradation and changes in the microenvironment following initial mast cell secretion, the mast cell populations may change significantly in number, phenotype and function. In tumor models, mast cells have been shown to play a decisive role in inducing the angiogenic switch which precedes malignant transformation. There is, moreover, strong evidence that mast cells significantly influence angiogenesis and thus growth and progression in human cancers.     

Mast cells in human lungs

Mast cells were stained deeply in human lung tissue with acidic toluidine blue to obtain maximum numbers possible in paraffin sections. One hundred high-power fields were counted per section, and mean and median values summarized as mast cells per mm2. Immersion-fixed samples of fresh lung tissue (not bronchi) were taken as controls from seven patients after surgery, and showed mean values of 44.7 mast cells per mm2 after formalin fixation, and 51.9 per mm2 after Carnoy's fixative. Mast cell heterogeneity may explain these differences, but so could random variation between counts. In two patients with extrinsic allergic alveolitis (hypersensitivity pneumonitis), fresh lung tissue from open lung biopsies showed raised values of 90.8 and 101.9 mast cells per mm2, matching the high mast cell counts reported in bronchopulmonary lavage fluid in the condition. Control post-mortem lung tissue from two patients dying of non-pulmonary diseases showed mean values of 26.1 and 50.6 mast cells per mm2. Post-mortem lung tissue from three patients dying of asthma showed very low mean values of 4.7, 5.7, and 5.9 mast cells per mm2. Low mast cell counts due to severe degranulation have been reported before in the bronchi in asthma deaths, but not, to our knowledge, in the lung parenchyma. This finding implies a wider area of mediator release, and helps to explain the severity of the acute attack, and the fatal outcome.     

Mast cells in calcific aortic stenosis

In developed countries, calcific aortic stenosis (CAS) has become the most common acquired valvular disease and reason for aortic valve replacement. It is considered a form of atherosclerosis and, like the latter, of inflammatory origin, with presence in the calcified aortic valves of blood vessels, lymphatics, lymphocytes, plasma cells, histiocytes, and sometimes also of metaplastic bone tissue. This study is aimed at examining the presence of CD117 – positive mast cells in CAS. In 56 examined calcified aortic valves excised by cardiac surgery, mast cells were constantly present as a part of the polymorphous cellular infiltrate; in individual cases, their numbers were 1–90 (median 24). The numbers were significantly higher in the congenitally malformed/bicuspid valves (median 40) than in the tricuspid ones (median 20). In valves with presence of metaplastic bone, mast cells were significantly more numerous (median 42) than in those without metaplasia (median 20). In 12 normal aortic valves obtained at autopsies, the numbers of mast cells were 4–21 (median 11). Discussed is a possible role of mast cells in pathogenesis of CAS.     

人脐血干细胞体外诱导为肥大细胞的研究进展

Mast cells (MCs) play a key role in the pathogenesis of allergic diseases. Tissue MCs are originated from hematopoiefic stem cells in bone marrow. In recent years, it was reported that human mast cells could be differentiated from stem cells of umbilical cord blood. In this review, we summarize the development in this novel area.     

Mast cells: Versatile gatekeepers of pain

Mast cells are important first responders in protective pain responses that provoke withdrawal from intense, noxious environmental stimuli, in part because of their sentinel location in tissue–environment interfaces. In chronic pain disorders, the proximity of mast cells to nerves potentiates critical molecular cross-talk between these two cell types that results in their synergistic contribution to the initiation and propagation of long-term changes in pain responses via intricate signal networks of neurotransmitters, cytokines and adhesion molecules. Both in rodent models of inflammatory pain and chronic pain disorders, as well as in increasing evidence from the clinic, it is abundantly clear that understanding the mast cell-mediated mechanisms underlying protective and maladaptive pain cascades will lead to improved understanding of mast cell biology as well as the development of novel, targeted therapies for the treatment and management of debilitating pain conditions.     

Mast cells in the mammalian area postrema

Summary Mast cells, identified by metachromasia of perikarya in material fixed by two-step perfusion with Bouin's solution, were studied in the area postrema of 25 mammalian species. (A) The appearance of mast cells varied greatly, and when the population of these cells was high, they were predominantly of the pale type with pyknotic nuclei. (B) The mast cells tended to accumulate near the ventricular surface in primates and carnivores, while in other species the distribution was diffuse. (C) They were found in large numbers, up to 16 000, in such adult animals as the chimpanzee, stumptailed and cynomolgus monkeys, dog and cat, and in smaller numbers in the capuchin monkey, opossum, agouti and acuchi, but more rarely or not at all in most rodents and the lagomorph. No mast cells occurred in the mulatta monkey, with the exception of a 28-year-old female. (D) In the stumptailed and cynomolgus monkeys, the number increased with weight of the animal and, in both the cynomolgus monkey (already present at birth) and the cat, with age; even then, in individual instances, mast cells were absent. Infection was considered as a factor contributing to an increase in number, but study of pathogen-free cynomolgus monkeys was inconclusive. Appearance and content of mast cells in monkeys and/or cats were not affected by dietary regimen, treatment with reserpine, L-histidine, cortisone or thyrotropic hormone, or castration. —At this stage of experience, the role of mast cells in the area postrema remains enigmatic.Results of a pilot survey were presented at the Anatomical Institute of the University in Oslo, Norway, September 14, 1970 (Cammermeyer, 1971 a).     

Mast cells in allergy and infection: Versatile effector and regulatory cells in innate and adaptive immunity

Mast cells are widely distributed in tissues, particularly near surfaces exposed to the environment. Mast cells can be activated to secrete diverse mediators and cytokines by IgE and specific Ag and many other stimuli, including products derived from either pathogens or the host during innate immune responses. Although mast cells are best known for their role in IgE‐associated allergic disorders, mast cells can also exacerbate models of autoimmunity, enhance the sensitization and/or effector phases of certain cutaneous contact hypersensitivity responses, and increase inflammation and mortality during some severe bacterial infections. In other settings, however, mast cells can limit inflammation and tissue injury: mast cells promote host resistance in certain models of bacterial or parasite infection, limit pathology during some acquired immune responses to environmental Ag, including examples of severe contact hypersensitivity, and have adjuvant‐like properties that can enhance the development of protective immunity against pathogens. These and other findings suggest that mast cells occupy a critical niche at the interface of innate and acquired immunity, where, depending on circumstances that remain to be fully understood, mast cells may function to perturb or help to restore homeostasis (or both), with consequences that can either promote health or contribute to disease.     

肥大细胞在多发性硬化中的发病机制研究进展

多发性硬化(MS)是最常见的中枢神经系统炎性脱髓鞘疾病之一.实验性自身免疫性脑脊髓炎(EAE)模型和MS具有相似的病理生理过程,是MS研究的经典模型.目前认为,MS的发病与遗传、环境及患者机体自身免疫状态等多因素有关.肥大细胞可以分泌多种炎症介质和细胞因子而发挥重要的免疫防御作用.研究表明,肥大细胞参与并调控了MS和EAE进展中的多个阶段,但机制尚未完全阐明.因此,研究肥大细胞在MS中的发病机制具有重要意义.     

Mast cell numbers in appendices with threadworm infestation

A study has been made of mast cells (MC) in surgically resected appendices using a long toluidine blue (LTB) staining method. The numbers of MC in measured areas of both mucosa and submucosa/muscularis were counted and comparisons made between 22 appendices containing threadworms and 22 which were histologically normal. There was considerable variation in MC numbers from case to case and the patients aged under 15 as a group had a higher mean number of mucosal MC than the older patients. The reasons for the high individual variation could not be identified from the histological sections, and no correlation was found between MC numbers and the presence of threadworms.     

Mast cells in allergy: innate instructors of adaptive responses

The function of mast cells as effector cells in allergy has been extensively studied. However, increasing insight into mast cell physiology has revealed new mast cell functions and has introduced mast cells as key players in the regulation of innate as well as adaptive immunity. For example, mast cells have recently been found to express Toll-like receptors (TLRs), which enable them to participate in the innate immune response against pathogens. Furthermore, mast cells have been reported to interact with B cells, dendritic cells and T cells and thereby modulate the direction of an adaptive immune response. Finally, recent documentation that mast cells express functional MHC class II and costimulatory molecules and release immunologically active exosomes, has raised the possibility that mast cells also engage in (as yet) poorly understood antigen presentation functions. In this review, we explore the hypothesis that mast cells serve as central mediators between innate and adaptive immunity, rather as pure effector cells, during allergic innate responses.     

Antibodies to hepatitis E virus among chinese patients with acute hepatitis in Taiwan

The prevalence of antibodies to hepatitis E virus (anti-HEV) was investigated in patients with acute hepatitis, and correlated with the clinical features. Sera from 110 patients with acute hepatitis and 60 healthy controls were tested for anti-HEV, antibody to hepatitis C virus (anti-HCV), and hepatitis B surface antigen (HBsAg). There were significant differences in the prevalence of anti-HEV, anti-HCV, and HBsAg between patients and controls (21.8% vs. 0%, 16.3% vs. 1.6% and 58.1% vs. 18.0%, respectively). Anti-HEV was detected in 6 (25.0%) of 24 patients with anti-HCV, 6 (9.3%) of 64 patients with HBsAg, and another 6 (22.2%) of 27 patients with acute hepatitis non-A, non-B, non-C. Anti-HEV was found in 15 men and three women, whose ages ranged from 34 to 75 (median, 57) years old. The median age of patients with anti-HEV was older than that in patients without this antibody (57 vs. 38 years; P = 0.001). The prevalence of anti-HEV in patients with anti-HCV alone (35.2%) was higher than that (11.1%) in patients with HBsAg alone (P = 0.03). Compared to patients without anti-HEV, HEV-infected patients had a higher frequency of travel to a foreign country (P = 0.0001), had a lower HBsAg rate (P = 0.019), and had higher serum alkaline phosphatase levels (P = 0.04) and gamma-glutamyl transpeptidase levels (P = 0.01). In conclusion, HEV infection occurs in 22.2% of patients with acute hepatitis non-A, non-B, non-C. HEV superinfection may occur in patients with chronic hepatitis B or C virus infection. © 1994 Wiley-Liss, Inc.     

Mechanisms of liver cell damage in acute hepatitis B

Markers of hepatitis B viral infection and the evolution of immune response to these were compared with serum alanine aminotransferase (ALT) levels in adult male and non-pregnant and pregnant female patients with acute hepatitis B from the time of onset of disease to the seventh week. In the adult male and non-pregnant female patients, the peak ALT levels of about 360 IU/litre, seen at the time of onset, gradually declined during the course of the disease. Significantly, even in the seventh week, the median ALT level was abnormal (80 IU/litre). In contrast, the disease was mild in pregnant patients and the ALT levels declined rapidly, returning to normal by the third week. Markers associated with HBV replication, i.e., serum HBV-DNA and HBeAg, declined early in the course of the disease in both groups. The anti-HBc-IgM and anti-HBe responses were well evolved early in the course of the disease in both groups. HBsAg was present in the serum in large amounts (1-1.5 X 10(4) AU/100 microliter) early in the course of the disease and remained so up to the seventh week. Even the pregnant patients who had recovered clinically by the fourth week continued to have HBsAg in their sera in large amounts in spite of normal ALT levels. LMI and LTT responses to HBsAg, which were practically absent in the first week, gradually increased to a peak during the fourth week and remained elevated up to the seventh week in adult male and non-pregnant female patients. In contrast, LMI response to HBsAg was absent in pregnant patients with acute hepatitis B even up to the fourth week Thus, continued liver cell necrosis after the fourth week, as indicated by raised ALT levels, may be associated with T cell responses to HBsAg.     

Stem cells in experimental chronic hepatitis

We studied the state of the pools of mesenchymal precursor cells in the bone marrow and peripheral blood and the dynamics of regional precursor cells in the liver in experimental chronic hepatitis. We showed that bone marrow mesenchymal stem cells are involved in liver regeneration in its chronic disease. Our results suggest that these mechanisms are insufficient for the recovery of liver tissue. __________ Translated from Kletochnye Tehnologii v Biologii i Medicine, No. 1, pp. 26–29, January, 2007     

Mast cells and postnatal topographic anomalies in mammalian subfornical body and supraoptic crest

Summary In the central nervous system of 22 animal species, mast cells occur (1) in both the subfornical body and the supraoptic crest in chimpanzee, stumpatailed monkey, agouti and flying squirrel and in cynomolgus monkey from 1 day of age; (2) in the subfornical body in paca, ground squirrel, woodchuck and prairie dog; and (3) in the supraoptic crest in cats from 2 days of age through the fourth month, and capybara. The medial habenular nucleus and the area postrema contain mast cells in many of the animals, but differences in number with species and with age do not follow the same pattern as in the above regions. Not infrequently, the thalamus has a considerable number of mast cells, and occasionally other regions, such as the dentate nuclei and the medulla oblongata, have a few mast cells.The number of mast cells, amounting to several hundreds in the circumventricular regions, varies with region, species, individual animal and age. The marked qualitative and quantitative differences, which complicate interpretation of experimental results, are associated with differences in functional requirements; the migratory faculty of the mast cell would enable each of its many biogenic amines to act separately on specific elements at different sites as demand arises.Study of newborn animals disclosed mitotic cells in several of the circumventricular regions. The formation of dysmitotic elements, as an expression of anomalous mitosis, may be the cause of disproportionate growth of the tissue and the overlying ependyma, whereby aberrations in the development of the ventricular wall ensue.     

Mast cells in type 2 skin inflammation: Maintenance and function

Mast cells (MCs) are immune cells residing in tissues and playing indispensable roles in maintaining homeostasis and inflammatory states. Skin lesions associated with atopic dermatitis (AD) and type 2 skin inflammation display an increment in MCs, which have both pro- and anti-inflammatory effects. The direct and indirect activations of skin MCs by environmental factors such as Staphylococcus aureus can instigate type 2 skin inflammation in AD with poorly understood mechanisms. Furthermore, both IgE-dependent and -independent degranulation of MCs contribute to pruritus in AD. Conversely, MCs suppress type 2 skin inflammation by promoting Treg expansion through IL-2 secretion in the spleen. Moreover, skin MCs can upregulate gene expression involved in skin barrier function, thus mitigating AD-like inflammation. These functional variances of MCs in AD could stem from differences in experimental systems, their localization, and origins. In this review, we will focus on how MCs are maintained in the skin under homeostatic and inflammatory conditions, and how they are involved in the pathogenesis of type 2 skin inflammation.     

Novel Strategies to Target Mast Cells in Disease

Mast cells (MCs) are versatile effector cells of the immune system, characterized by a large content of secretory granules containing a variety of inflammatory mediators. They are implicated in the host protection toward various external insults, but are mostly well known for their detrimental impact on a variety of pathological conditions, including allergic disorders such as asthma and a range of additional disease settings. Based on this, there is currently a large demand for therapeutic regimens that can dampen the detrimental impact of MCs in these respective pathological conditions. This can be accomplished by several strategies, including targeting of individual mediators released by MCs, blockade of receptors for MC-released compounds, inhibition of MC activation, limiting mast cell growth or by inducing mast cell apoptosis. Here, we review the currently available and emerging regimens to interfere with harmful mast cell activities in asthma and other pathological settings and discuss the advantages and limitations of such strategies.