• Klíčová slova
• MAST CELLS *,
• MeSH
• hematologické nádory * MeSH
• lidé MeSH
• mastocytom * MeSH
• mastocyty * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• LIPIDS/metabolism *, MAST CELLS/physiology *,
• MeSH
• fyziologie buňky * MeSH
• lidé MeSH
• lipidy * MeSH
• mastocyty fyziologie   MeSH
• metabolismus lipidů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lipidy * MeSH

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.

• Klíčová slova
• CD117, Calcific aortic stenosis, Mast cells, Pathogenesis,
• MeSH
• aortální chlopeň patologie   MeSH
• aortální stenóza patologie   MeSH
• B-lymfocyty metabolismus   MeSH
• imunoglobuliny metabolismus   MeSH
• lidé MeSH
• mastocyty patologie   MeSH
• pitva metody   MeSH
• zánět metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunoglobuliny MeSH

The immune checkpoint inhibitors have revolutionized cancer immunotherapy. These inhibitors are game changers in many cancers and for many patients, sometimes show unprecedented therapeutic efficacy. However, their therapeutic efficacy is largely limited in many solid tumors where the tumor-controlled immune microenvironment prevents the immune system from efficiently reaching, recognizing, and eliminating cancer cells. The tumor immune microenvironment is largely orchestrated by immune cells through which tumors gain resistance against the immune system. Among these cells are mast cells and dendritic cells. Both cell types possess enormous capabilities to shape the immune microenvironment. These capabilities stage these cells as cellular checkpoints in the immune microenvironment. Regaining control over these cells in the tumor microenvironment can open new avenues for breaking the resistance of solid tumors to immunotherapy. In this review, we will discuss mast cells and dendritic cells in the context of solid tumors and how these immune cells can, alone or in cooperation, modulate the solid tumor resistance to the immune system. We will also discuss how this modulation could be used in novel immunotherapeutic modalities to weaken the solid tumor resistance to the immune system. This weakening could then help other immunotherapeutic modalities engage against these tumors more efficiently.

• Klíčová slova
• cellular checkpoint, dendritic cells, immunotherapy, mast cells,
• MeSH
• dendritické buňky patologie   MeSH
• imunoterapie MeSH
• inhibitory kontrolních bodů MeSH
• lidé MeSH
• mastocyty * patologie   MeSH
• nádorové mikroprostředí MeSH
• nádory * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• inhibitory kontrolních bodů MeSH

Mast cells play crucial roles in both innate and adaptive arms of the immune system. Along with basophils, mast cells are essential effector cells for allergic inflammation that causes asthma, allergic rhinitis, food allergy and atopic dermatitis. Mast cells are usually increased in inflammatory sites of allergy and, upon activation, release various chemical, lipid, peptide and protein mediators of allergic reactions. Since antigen/immunoglobulin E (IgE)-mediated activation of these cells is a central event to trigger allergic reactions, innumerable studies have been conducted on how these cells are activated through cross-linking of the high-affinity IgE receptor (FcεRI). Development of mature mast cells from their progenitor cells is under the influence of several growth factors, of which the stem cell factor (SCF) seems to be the most important. Therefore, how SCF induces mast cell development and activation via its receptor, KIT, has been studied extensively, including a cross-talk between KIT and FcεRI signaling pathways. Although our understanding of the signaling mechanisms of the FcεRI and KIT pathways is far from complete, pharmaceutical applications of the knowledge about these pathways are underway. This review will focus on recent progresses in FcεRI and KIT signaling and chemotaxis.

• Klíčová slova
• Chemotaxis, IgE receptor, KIT receptor, Mast cell, Plasma membrane, Signal transduction,
• MeSH
• chemotaxe * účinky léků   MeSH
• lidé MeSH
• mastocyty cytologie   účinky léků   MeSH
• signální transdukce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH

Dendritic cells (DCs) and mast cells (MCs) are key players of the immune system, often coming in close proximity in peripheral tissues. The interplay of these cells is, however, still poorly understood, especially with regards to human cells. The reason for that is the absence of a well established in vitro human cell-based study system that would allow a simultaneous preparation of both cell types. In this study, we show a method for simultaneous generation of DCs and MCs from CD34+ stem cell progenitors that were isolated from the non-adherent fraction of non-mobilized peripheral blood mononuclear cells of healthy donors. We observed that combining stem cells factor (SCF), IL-3 and GM-CSF in serum-free StemPro-34 medium allowed CD34+ cells isolated from an equivalent of 450 ml of peripheral blood to expand to 10-92 × 106 cells after 7 weeks of culturing. These cultures comprised of 6-53% of DCs and 1-21% of MCs as determined by the expression of, respectively, CD11c/HLA-DR or CD117/FcεRI. The DCs were CD1a-CD14-, did not express co-stimulatory molecules CD80 and CD83 and chemokine receptor CCR7. However, the DCs expressed co-stimulatory molecule CD86, and had a capacity to uptake dextran, phagocyte latex particles and induce alloreactivity. MCs, on the other hand, degranulated after crosslinking of FcεRI-bound IgE as determined by the externalization of CD107b. Collectively, our data show that CD34+-derived human DCs and MCs can be generated in a single culture using CD34+ cells isolated from non-mobilized human peripheral blood and that this method may allow ex vivo studies on DC-MC interplay in human system.

• Klíčová slova
• CD34, Dendritic cells, Mast cells,
• MeSH
• antigeny CD34 metabolismus   MeSH
• buněčná diferenciace MeSH
• degranulace buněk imunologie   MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• dextrany imunologie   MeSH
• faktor růstu kmenových buněk metabolismus   MeSH
• faktor stimulující granulocyto-makrofágové kolonie metabolismus   MeSH
• kmenové buňky z periferní krve fyziologie   MeSH
• kultivační média bez séra metabolismus   MeSH
• leukocyty mononukleární MeSH
• lidé MeSH
• mastocyty imunologie   MeSH
• mezibuněčná komunikace imunologie   MeSH
• primární buněčná kultura metody   MeSH
• průtoková cytometrie metody   MeSH
• rekombinantní proteiny metabolismus   MeSH
• separace buněk metody   MeSH
• vrstva buffy coat cytologie   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD34 MeSH
• dextrany MeSH
• faktor růstu kmenových buněk MeSH
• faktor stimulující granulocyto-makrofágové kolonie MeSH
• kultivační média bez séra MeSH
• rekombinantní proteiny MeSH

BACKGROUND: The prognostic significance of mast cells and different phenotypes of macrophages in the microenvironment of hepatocellular carcinoma (HCC) following resection is unclear. We aimed in this study to assess the local distribution of infiltrating macrophages and mast cells of specific phenotypes in tissues of HCC and to evaluate their prognostic values for survival of post-surgical patients. METHODS: The clinicopathological and follow-up data of 70 patients with HCC, who underwent curative resection of tumor from 1997 to 2019, were collected. The infiltration of CD68+ and CD163+ macrophages and CD117+ mast cells was assessed immunohistochemically in representative resected specimens of HCC and adjacent tissues. The area fraction (AF) of positively stained cells was estimated automatically using QuPath image analysis software in several regions, such as tumor center (TC), inner margin (IM), outer margin (OM), and peritumor (PT) area. The prognostic significance of immune cells, individually and in associations, for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) was evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: High AF of CD68+ macrophages in TC and IM and high AF of mast cells in IM and PT area were associated with a longer DFS. High AF of CD163+ macrophages in PT area correlated with a shorter DFS. Patients from CD163TChigh & CD68TClow group had a shorter DFS compared to all the rest of the groups, and cases with CD163IMlow & CD68IMhigh demonstrated significantly longer DFS compared to low AF of both markers. Patients from CD68IMhigh & CD163PTlow group, CD117IMhigh & CD163PTlow group, and CD117PThigh & CD163PTlow group had a significantly longer DFS compared to all other combinations of respective cells. CONCLUSIONS: The individual prognostic impact of CD68+ and CD163+ macrophages and mast cells in the microenvironment of HCC after resection depends on their abundance and location, whereas the cumulative impact is built upon combination of different cell phenotypes within and between regions.

• Klíčová slova
• Disease-free survival, Hepatocellular carcinoma, Inner margin, Mast cells, Peritumor area, Tumor-infiltrating macrophages,
• MeSH
• hepatocelulární karcinom * patologie   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé MeSH
• makrofágy patologie   MeSH
• mastocyty patologie   MeSH
• nádorové mikroprostředí MeSH
• nádory jater * patologie   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The antigen-mediated activation of mast cells initiates signaling events leading to their degranulation, to the release of inflammatory mediators, and to the synthesis of cytokines and chemokines. Although rapid and transient microtubule reorganization during activation has been described, the molecular mechanisms that control their rearrangement are largely unknown. Microtubule nucleation is mediated by γ-tubulin complexes. In this study, we report on the regulation of microtubule nucleation in bone marrow-derived mast cells (BMMCs) by Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1 (SHP-1; Ptpn6). Reciprocal immunoprecipitation experiments and pull-down assays revealed that SHP-1 is present in complexes containing γ-tubulin complex proteins and protein tyrosine kinase Syk. Microtubule regrowth experiments in cells with deleted SHP-1 showed a stimulation of microtubule nucleation, and phenotypic rescue experiments confirmed that SHP-1 represents a negative regulator of microtubule nucleation in BMMCs. Moreover, the inhibition of the SHP-1 activity by inhibitors TPI-1 and NSC87877 also augmented microtubule nucleation. The regulation was due to changes in γ-tubulin accumulation. Further experiments with antigen-activated cells showed that the deletion of SHP-1 stimulated the generation of microtubule protrusions, the activity of Syk kinase, and degranulation. Our data suggest a novel mechanism for the suppression of microtubule formation in the later stages of mast cell activation.

• Klíčová slova
• SHP-1 tyrosine phosphatase, bone marrow-derived mast cells, cell activation, microtubule nucleation, γ-tubulin complexes,
• MeSH
• degranulace buněk MeSH
• HEK293 buňky MeSH
• kinasa Syk metabolismus   MeSH
• lidé MeSH
• mastocyty cytologie   metabolismus   MeSH
• MFC-7 buňky MeSH
• mikrotubuly metabolismus   MeSH
• myši MeSH
• tubulin metabolismus   MeSH
• tyrosinfosfatasa nereceptorového typu 6 antagonisté a inhibitory   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kinasa Syk MeSH
• Ptpn6 protein, mouse MeSH Prohlížeč
• Syk protein, mouse MeSH Prohlížeč
• tubulin MeSH
• tyrosinfosfatasa nereceptorového typu 6 MeSH

An almost twenty-fold increase in mast cell concentration was observed in the spleens of BALB/c mice after sublethal X-irradiation. Repopulation with bone marrow cells abolished this effect.

• MeSH
• časové faktory MeSH
• kostní dřeň účinky záření   MeSH
• lymfocyty cytologie   účinky záření   MeSH
• mastocyty cytologie   účinky záření   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries. Mast cells have an important role in many inflammatory diseases and they are also involved in tissue remodeling. Tissue hypoxia is associated with mast cell activation and the release of proteolytic enzymes, angiogenic and growth factors which mediate tissue destruction and remodeling in a variety of physiological and pathological conditions. Here we focused on the role of mast cells in the pathogenesis of hypoxic pulmonary hypertension from the past to the present.

• MeSH
• hypoxie buňky MeSH
• lidé MeSH
• mastocyty metabolismus   MeSH
• plicní hypertenze metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH