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 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 f...     

Human bone marrow mast cells in systemic mast cell disease

In a case of systemic mast cell disease with moderate bone marrow involvement, we studied the sensitivity of mast cell cationic dye-binding to formaldehyde fixation, as well as the mast cell ultrastructure, so as to determine whether these cells possess characteristics of mucosal mast cells. This histochemical method has proved to be one of the few which reveal heterogeneity of the mast cells in human intestine. Even though rat bone marrow mast cells have been shown to belong to the mucosal mast cell compartment, we have found no difference in mast cell counts in samples fixed either in formaldehyde or Carnoy's fixative. The ultrastructure did not show major differences with cutaneous mast cells. A few cells presented two nuclei, suggesting mitotic division of mature mast cells in bone marrow.     

FcγR-dependent apoptosis regulates tissue persistence of mucosal and connective tissue mast cells

Rodent mast cells can be divided into two major subtypes: the mucosal mast cell (MMC) and the connective tissue mast cell (CTMC). A decade-old observation revealed a longer lifespan for CTMC compared with MMC. The precise mechanisms underlying such differential tissue persistence of mast cell subsets have not been described. In this study, we have discovered that mast cells expressing only one receptor, either FcγRIIB or FcγRIIIA, underwent caspase-independent apoptosis in response to IgG immune complex treatment. Lower frequencies of CTMC in mice that lacked either FcγRIIB or FcγRIIIA compared with WT mice were recorded, especially in aged mice. We proposed that this paradigm of FcγR-mediated mast cell apoptosis could account for the more robust persistence of CTMC, which express both FcγRIIB and FcγRIIIA, than MMC, which express only FcγRIIB. Importantly, we reproduced these results using a mast cell engraftment model, which ruled out possible confounding effects of mast cell recruitment or FcγR expression by other cells on mast cell number regulation. In conclusion, our work has uncovered an FcγR-dependent mast cell number regulation paradigm that might provide a mechanistic explanation for the long-observed differential mast cell subset persistence in tissues.     

肥大细胞在食管癌的特征—组织化学与电镜的观察

对１８例食管癌的肥大细胞进行了组织化学与电镜下的观察，发现在癌组织边缘，癌组织内血管附近结缔组织中及癌旁组织的上皮下与粘膜下层都出现了大量肥大细胞。这些肥大细胞在Ａｌｃｉａｎ蓝，藏红染色，其颗粒主要为Ａｌｃｉａｎ蓝阳性。在显示肝素的硫酸小檗碱荧光反应，在癌组织及旁组织的肥大细胞大多都是阴性。有极少数的癌旁组织的肥大细胞呈黄色荧光反应。电镜下，肥大细胞颗料中具有Ｔ肥大细胞特征的多个涡卷状结构。有些肥     

Committed mast cell progenitors in mouse blood differ in maturity between Th1 and Th2 strains

Mast cell progenitors (MCp) leave the bone marrow and migrate to peripheral tissues where they mature. Although the existence of committed MCp in adult mouse and human blood has been postulated, they have never been found. We have isolated a rare population of cells in adult mouse blood, committed to the mast cell lineage. These were identified as lineage⁻ c‐kit^hi ST2⁺ integrin β7^hi CD16/32^hi cells. Moreover, a major difference in maturity of these cells based on FcεRI expression was observed between the Th2‐prone BALB/c strain and the Th1‐prone C57BL/6 strain (66% vs 25% FcεRI⁺, respectively). Therefore, the choice of mouse strain is critical when studying disease models such as experimental asthma where mast cells and their progenitors are involved.     

肥大细胞与成纤维细胞功能关系的光镜与电镜研究

通过对正常人体皮肤真皮与胶原纤维大量增生的疾患的真皮组织的光镜与电镜的比较观察,发现在病因不同,而都有胶原纤维大量增生的系统性硬皮病与皮肤纤维瘤的真皮组织中,肥大细胞都比正常时显著增多(P<0.01),而且肥大细胞常与成纤维细胞紧密相靠接,这里的肥大细胞脱颗粒现象也增多。从颗粒的超微结构特征所示,这些肥大细胞以未成熟的T型肥大细胞为主。以上提示:肥大细胞在调节成纤维细胞产生胶原纤维的功能上具有重要意义。     

Expression of the c-kit gene product in normal and neoplastic mast cells but not in neoplastic basophil/mast cell precursors from chronic myelogenous leukaemia

The expression of the c-kit gene product has been examined in normal mast cells, mast cell neoplasms, and basophil/mast cell precursors obtained from patients with chronic myelogenous leukaemia (CML). Formalin-fixed, paraffin-embedded sections or smears fixed with formalin vapour were studied by immunohistochemical methods, using a polyclonal antibody against the c-kit gene product. Normal and neoplastic mast cells showed a positive immunoreaction for c-kit gene product, but neoplastic basophil/mast cell precursors from CML patients lacked c-kit gene product by immunohistochemical and flow cytometric methods, even in cells having mast cell granules, together with or without basophil granules. Mast cell tryptase was, however, expressed in normal and neoplastic mast cells and basophil/mast cell precursors containing mast cell granules. In addition, cells of monocyte/macrophage lineage lacked c-kit gene product. These findings indicate that the c-kit gene product may play an important role in the development and function of mast cell but not of cell of basophil and monocyte/macrophage lineage.     

人腭扁桃体肥大细胞的性质—免疫组化法研究

收集手术切除的人腭扁桃体标本６例，常规石蜡切片，分别以血管活性肠肽、阿尔新蓝－番红花红、长时间甲苯胺蓝和普通甲苯胺蓝染色观察肥大细胞。结果显示：肥大细胞呈血管活性肠肽免疫反应阳性，分布于淋巴小结中央及周围的弥散淋巴组织、被膜及小梁的结缔组织、固有层和小血管周围。阿尔新蓝－番红花红染色呈浅蓝色颗粒。长时间甲苯胺蓝染色显示的肥大细胞数目较多，颗粒为深蓝色。普通甲苯胺蓝染色未以显示肥大细胞。结果提示，人     

不同年龄人牙龈肥大细胞的组织化学和电镜研究

取４０例临床下沉的人牙龈组织，按年龄不同分为２－１６岁，１７－６０岁，６１－６５岁三组，对每组肥大细胞进行光镜与电镜观察，结果发现：随着年龄增长，肥大细胞数量表现为由少到多，又由多到少的变化：Ａｌｃｉａｎ蓝－藏红组化染色后，三组均以蓝染的肥大细胞为主 ，呈红蓝混合色的肥细胞亦随年龄增长出现由少到多，又由多到少的变化；临界电解质浓度的测定结果显示，三组均较高，但随年龄增长仍有增高趋势；电镜下多数肥大     

人胎儿胃肥大细胞的研究

观察了 40例不同胎龄胎儿胃底部两型肥大细胞发育、数量及分布和胃底部发育的关系 ,并探讨了甲醛固定对 CTMC和 MMC染色效应的影响。发现人胎儿胃 CTMC出现于受精后 13～ 16周的粘膜下层等处 ,主要分布在胃粘膜固有层近粘膜肌处 ,数量随粘膜层胃底腺及粘膜肌等结构的发育而增加。两型肥大细胞对甲醛固定的反应无明显差异。本文就肥大细胞在胃底部发育过程中的意义进行了讨论     

Mast Cell Interaction with Tumor Cells in Small Early Gastric Cancer: Ultrastructural Observations

The authors studied the mast cells by light and electron microscopy in four small intramucosal early gastric cancers (EGC). Mast cells were found in the tumor stroma and among neoplastic cells of adenocarcinoma glands. Stromal and ad-enocarcinoma-infiltrating mast cells were ultrastructurally identified as T mast cells, and exhibited anaphylactic or piecemeal degranulation. Tumor cells in intimate contact with mast cells showed no cytopathic changes. These data do not support a mast cell-mediated cancer lysis, such as that reported in some systems in vitro. The interepithelial localization of T mast cell in adenocarcinoma glands is similar to that observed in some disease states, including interstitial cystitis, fibrotic lung disorders, and mucosal allergic reaction. The findings suggest that T mast cells may be involved in the pathophysiology of the host reaction to small intramucosal EGC.     

Protease–proteoglycan complexes of mouse and human mast cells and importance of their β-tryptase–heparin complexes in inflammation and innate immunity

Summary:  Approximately 50% of the weight of a mature mast cell (MC) consists of varied neutral proteases stored in the cell's secretory granules ionically bound to serglycin proteoglycans that contain heparin and/or chondroitin sulfate E/diB chains. Mouse MCs express the exopeptidase carboxypeptidase A3 and at least 15 serine proteases [designated as mouse MC protease (mMCP) 1–11, transmembrane tryptase/tryptase γ/protease serine member S (Prss) 31, cathepsin G, granzyme B, and neuropsin/Prss19]. mMCP-6, mMCP-7, mMCP-11/Prss34, and Prss31 are the four members of the chromosome 17A3.3 family of tryptases that are preferentially expressed in MCs. One of the challenges ahead is to understand why MCs express so many different protease–proteoglycan macromolecular complexes. MC-like cells that contain tryptase–heparin complexes in their secretory granules have been identified in the Ciona intestinalis and Styela plicata urochordates that appeared approximately 500 million years ago. Because sea squirts lack B cells and T cells, it is likely that MCs and their tryptase–proteoglycan granule mediators initially appeared in lower organisms as part of their innate immune system. The conservation of MCs throughout evolution suggests that some of these protease–proteoglycan complexes are essential to our survival. In support of this conclusion, no human has been identified that lacks MCs. Moreover, transgenic mice lacking the β-tryptase mMCP-6 are unable to combat a Klebsiella pneumoniae infection effectively. Here we summarize the nature and function of some of the tryptase–serglycin proteoglycan complexes found in mouse and human MCs.     

Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis,heritability and diagnostics

Despite increasing understanding of its pathophysiology, the aetiology of systemic mast cell activation disease (MCAD) remains largely unknown. Research has shown that somatic mutations in kinases are necessary for the establishment of a clonal mast cell population, in particular mutations in the tyrosine kinase Kit and in enzymes and receptors with crucial involvement in the regulation of mast cell activity. However, other, as yet undetermined, abnormalities are necessary for the manifestation of clinical disease. The present article reviews molecular genetic research into the identification of disease‐associated genes and their mutational alterations. The authors also present novel data on familial systemic MCAD and review the associated literature. Finally, the importance of understanding the molecular basis of inherited mutations in terms of diagnostics and therapy is emphasized.     

Increased Mast Cell Density in Peritoneal Endometriosis Compared with Eutopic Endometrium with Endometriosis

PROBLEM: Factors regulating fibrosis in peritoneal endometriosis are poorly understood. We hypothesized that mast cell proteases may play a role in the process of fibrosis in peritoneal endometriosis. As the first step in examining the possible contribution of mast cells to fibrosis, we investigated their distribution in peritoneal endometriosis lesions according to their macroscopic appearance. METHOD OF STUDY: Mast cells were identified by immunohistochemistry using monoclonal antibody against mast cell tryptase on formalin-fixed, paraffin-embedded sections. Mast cell density (mean mast cell count per 0.13 mm² of stroma) was measured using a computerized image analysis system. RESULTS: Mast cell density was significantly increased in black peritoneal lesions compared with red peritoneal lesions in endometriosis. CONCLUSIONS: Mast cells may be involved in the pathogenesis of peritoneal endometriosis.     

小鼠哮喘模型气道上皮内肥大细胞数量增多

目的:观察小鼠哮喘模型气道卜皮内肥大细胞的数量,进一步阐明肥大细胞在鸡卵清蛋白(OVA)诱导的小鼠哮喘模型中的作用。方法:OVA诱导建立小鼠哮喘模型,H-E染色病理切片观察肺部感染情况,甲苯胺蓝染色法观察气道上皮内肥大细胞数量的变化。结果:哮喘模型组小鼠肺部炎症明显,在正常组和对照组小鼠气道上皮内没有发现肥大细胞,但在模型组小鼠气道上皮内肥大细胞的数量随OVA的激发次数增加而增多。结论:在OVA诱导的小鼠哮喘模型气道上皮内肥大细胞随着激发次数的增加而增多。气道上皮内肥大细胞在OVA诱导的哮喘模型起重要作用。     

P物质,血管活性肠肽和神经肽Y在大鼠舌肥大细胞内的定位研究

采用甲苯胺蓝染色和免疫组织化学ＡＢＣ方法，对大鼠舌组织中肥大细胞的分布，形态特点以及细胞内的Ｐ物质、血管活性肠肽和神经肽Ｙ的定位进行了研究。结果表明，大鼠舌组织内肥大细胞主要分布于固有层和肌层，多呈圆形，椭圆形或长梭形。经与甲苯胺蓝染色的相邻切片比较，几乎所有肥大细胞分别呈Ｐ物质、血管活性肠肽和神经肽Ｙ免疫反应阳性。提示：舌组织肥大细胞内Ｐ物质，血管活性肠肽和神经肽Ｙ等生物活性肽可能与其局部血液供