IgE-Mediated Activation of NK Cells Through FcγRIII
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Abstract NK cells express FcγRIII (CD16), which is responsible for IgG-dependent cell cytotoxicity and for production of several cytokines and chemokines. Whereas FcγRIII on NK cells is composed of both FcγRIIIα and FcRγ chains, that on mast cells is distinct from NK cells and made of FcγRIIIα, FcRβ, and FcRγ. Mast cells show degranulation and release several mediators, which cause anaphylactic responses upon cross-linking of FcγRIII as well as FcεRI with aggregated IgE. In this paper, we examined whether IgE activates NK cells through FcγRIII on their cell surface. We found that NK cells produce several cytokines and chemokines related to an allergic reaction upon IgE stimulation. Furthermore, NK cells exhibited cytotoxicity against IgE-coated target cells in an FcγRIII-dependent manner. These effects of IgE through FcγRIII were not observed in NK cells from FcRγ-deficient mice lacking FcγRIII expression. Collectively, these results demonstrate that NK cells can be activated with IgE through FcγRIII and exhibit both cytokine/chemokine production and Ab-dependent cell cytotoxicity. These data imply that not only mast cells but also NK cells may contribute to IgE-mediated allergic responses.The relations between human IgE and mouse peritoneal mast cells were studied in vitro. Non-heated human IgE sensitizes the mouse mast cells for degranulation on challenge with anti-human IgE. This capacity is lost after heating of human IgE at 56 degrees C. The degranulation only occurs in determined quantitative IgE-anti-IgE relationships, an excess of one or the other reagent inhibiting the reaction. Sensitization is practically instanteneous, and the degranulation is independent on the order of addition of the human IgE and anti-IgE. The human IgE can be removed from mouse peritoneal mast cells by a single washing. The results show that human IgE is unable to bind firmly to mouse peritoneal mast cells in vitro. It seems to induce the formation of biologically active human IgE-anti-human IgE complexes, which act on mouse mast cells and induce their degranulation.
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Abstract D iamant , B., P. G. K rüger and B. U vnäs . Local degranulation of individual rat peritoneal mast cells induced by compound 48/80 . Acta physiol. scand. 1970. 79 . 1–5. Degranulation of individual rat mast cells is shown to occur at the site of administration of compound 48/80 by the use of micropipets placed close to the mast cell membrane. Varying degree of degranulation can be induced. It is possible to induce repeated degranulation by local application of 48/80 to the same area of the cell at least four times. The results suggest that compound 48/80 acts directly on the cell membrane and this interaction seems to be the primary cause of the extrusion of granules.
Compound 48/80
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Abstract Mast cells are key effectors of allergic inflammation. IgE-mediated mast cell activation induces degranulation and inflammatory mediator release. Omalizumab (Xolair; Genentech Inc.) is a recombinant humanized monoclonal anti-IgE antibody that prevents IgE binding to its receptor, FcϵRI. Objective: We investigated the effects of omalizumab on IgE pre-sensitized human LAD2 mast cells. Methods: LAD2 degranulation was determined by β-hexosaminidase assay. Chemokine expression and prostaglandin synthesis was measured by quantitative PCR analysis and ELISA, respectively. IgE binding and FcϵRI expression was determined by flow cytometry. Results: Omalizumab pretreatment inhibited IgE binding to LAD2 cells and entirely prevented IgE-dependent upregulation of FcϵRI expression. In addition, omalizumab removed FcϵRI-prebound IgE as early as 24 hrs after treatment. After 5 days, bound IgE was reduced by 92%. Furthermore, omalizumab concomitantly reversed IgE-dependent FcϵRI upregulation by 49% 48 hrs post treatment and by 93% 5 days post treatment. Consequently, omalizumab attenuated ongoing IgE-mediated responses, reducing degranulation by 34%, chemokine expression up to 79% and prostaglandin synthesis by 34% after 7 days of omalizumab treatment. Conclusions: Omalizumab is able to remove pre-bound IgE from sensitized mast cells thereby reducing ongoing response to FcϵRI-dependent signals. This data suggests that omalizumab is an effective inhibitor of sensitized human mast cells.
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Prostaglandin D2
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Background: Although allergen‐specific IgE content in serum can be determined immunochemically, little is known about the relationship between this parameter and the strength of the degranulation response upon allergen triggering. Objectives: Analyse the degranulation capacity of immunochemically defined purified and serum IgE after challenge with anti‐IgE or allergen using a rat mast cell line (RBL) transfected with the α ‐chain of the human high‐affinity IgE receptor (Fc ɛ RI). Methods: Purified IgE specific for 4‐hydroxy‐3nitrophenylacetyl, purified IgE of unknown specificity, and sera from allergic patients sensitive to Dermatophagoides pteronyssinus and Dactylis glomerata were assessed. Degranulation was measured by a β ‐hexosaminidase release assay after anti‐IgE or allergen‐specific challenge. Results: For purified monoclonal IgE a significant correlation ( r = 0.97) was found between the proportion of bound allergen‐specific IgE and the strength of the degranulation response. In contrast, no correlation ( r = 0.27) was detected after sensitization with serum IgE. Conclusion: Our studies demonstrate that mast cell activation mediated through IgE from allergic patients is a result of complex relationships that are not only dependent on allergen‐specific IgE content but also relate to the capacity to efficiently sensitize and trigger the signalling responses that lead to degranulation.
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食物过敏症是世界范围的一个主要健康问题。桅杆房间在桅杆房间 degranulation 为需要广泛地被学习的立即的超敏性起一个很重要的作用。在这研究，一条途径被采取在 vitro 学习敏化的桅杆房间 degranulation 的特征，它与桅杆房间和动物模型的学习联系了。BALB/c 老鼠被几食物变应原分别地使免疫，然后，血和腹桅杆房间在不同时间点被收集。一颗动态决心在桅杆房间和 serumal IgE 之间被执行。顺序的时间点上的比较分析证明在敏化的 BALB/c 老鼠在桅杆房间 degranulation 和 IgE 抗体 titers 之间有靠近的巧合。而且，敏化的桅杆房间能在 vitro 对挑战实现特定的 degranulation，有趣，但是仔细， tropomyosins 导致了桅杆房间 degranulation 显示的生气反应。这很类似于在 vivo 抵抗变应原的 IgE。学习在桅杆房间上揭示了一些特征，来自敏化的 BALB/c 老鼠，在 vitro 的 degranulation。
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The action of a toxic substance (P-II fraction), extracted from the pedicellariae of Toxopneustes pileolus, on rat mesentery mast cells was studied. P-II fraction (3×10−5-2×l0−3g/ml) caused a dose-dependent degranulation of mesentery mast cells. The degranulation induced by P-II fraction (10−3g/ml) increased with time, while compound 4 8/80 (1μg/ml) caused a more rapid degranulation. These reactions were dependent on Ca2+ and temperature. When glucose (5.5mM) was omitted during the incubation step, the degranulation by P-II fraction was significantly reduced as compared to that of compound 48/80. On the other hand, the degranulation by P-II fraction was effectively potentiated by the addition of glucose (5.5mM), while the effect of compound 48/80 was unaltered. The effect of theophylline, adrenaline and DSCG on degranulation by P-II fraction or compound 48/80 was compared. In both cases, the degranulation was inhibited by these drugs. These results suggest that P-II fraction-induced degranulation differs from that of compound 48/80 in regards to time course and effects of glucose.
Compound 48/80
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Polychlorinated biphenyl
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Objective:Assess cytotoxicity of medical device with silver nanoparticles and assay the reason of the cytotoxicity.Method:The nine kinds of silver nanoparticle samples in three types were tested by MTT cytotoxicity method.Result:The test showed that the cytotoxic ity in 9 final samples all were grade 3 to 4;the gels and dressings which are semi-finished products without silver nanoparticles,were grade 1 of cytotoxicity;patches were grade 4 of cytotoxicity;patches without adhesive were grade 1 of cytotoxicity.Conclusion:Silver nanoparticle medical devices in the present test showed moderate or severe cytotoxicity.Gels or dressings only which without silver nanoparticle showed slightly cytotoxicity.Patches only which without silver nanoparticle showed severe cytotoxicity,and adhesive is the main reason of the cytotoxicity.Whether the severe cytotoxicity will induce persist cell damage,and the detail mechanisms of silver nanoparticle or adhesive-induced cytotoxicity need further investigation.
Silver nanoparticle
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Mouse and rat IgE fix firmly to the peritoneal mast cells from the other species, sensitizing them for anaphylactic reaction. Sensitization with IgE can be demonstrated by inducing degranulation either with specific antigens or with corresponding anti-IgE. Sensitization of rat mast cells by mouse IgE antibodies is more easily obtained than that of mouse mast cells by rat IgE antibodies. In this case, anti-IgE-induced degranulation is higher than antigen-induced degranulation. Heterologous sensitization by IgE is time requiring and temperature-dependent. Its kinetics depend upon IgE concentration. Cross-reactions between IgE from one species and anti-IgE from another species have been observed: anti-IgE for one species is able to neutralize PCA reaginic activity of sera from the other species; anti-rat IgE induces degranulation of mouse actively sensitized mast cells. The results suggest strongly that there exists a structural and functional similarity between the IgE molecules from the two species.
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