Induction of human basophil histamine release by a novel protein kinase C activator, sn-1,2-isopropylidene-3-decanoyl-glycerol (IpOCOC9): partial characterization of secretagogue characteristics

Human leukocytes were found to release histamine at exposure for the synthetic glyceride derivative sn-1,2-isopropylidene-3-decanoyl-glycerol (IpOCOC9). The following characteristics for the IpOCOC9-induced basophil histamine release were recorded. A. In the order of 25% of the cellular histamine content was extruded at 206 mumol/l and 45% at 690 mumol/l of the compound, respectively. B. Removal of extracellular Ca2+ variably affected IpOCOC9-triggered release. C. The presence of N-ethylmaleimide (10 mumol/l) or p-bromophenacylbromide (10 mumol/l) markedly reduced IpOCOC9-induced histamine release. D. The time course of the release triggered by IpOCOC9 was intermediate to those characterizing the release triggered by 4 beta-phorbol 12-myristate 13-acetate (PMA) and by formyl-methionyl-leucyl-phenylalanine (FMLP). E. Cells desensitized to IgE-receptor-mediated stimulation were hyperresponsive to stimulation with IpOCOC9. F. Cells treated with a low concentration of 2-deoxyglucose were not hyperresponsive to IpOCOC9. These data show that IpOCOC9, a PMN/leukocyte protein kinase C stimulator, acts as a non-cytotoxic secretagogue for human basophils with a mode of action which in some, but not all respects, mimics that of PMA. In particular, IpOCOC9-triggered release resembles that reported by other authors for hyperosmolar triggering of release by mannitol.     

Effects of Long-Term Treatment with Low Dose Cimetidine on Allergen-Induced Airway Responses and Selected Immunological Parameters in Atopic Asthmatics

Twenty asymptomatic atopic asthmatics were treated with either cimetidine 100 mg orally (13 patients) or placebo (7 patients) once a day for 4 weeks. Bronchial challenges were performed with the pertinent allergen immediately before and 2 and 4 weeks after the initiation of treatment and, finally, 4 weeks after the cessation of treatment. Before each challenge blood was drawn for the determination of specific IgE antibody levels (RAST procedure) and total IgE (PRIST), allergen- and anti-IgE-induced basophil histamine release, and mitogen-induced lymphocyte (3H)-thymidine incorporation. Patients treated with cimetidine were found to be significantly (P less than 0.05) less responsive to bronchial allergen challenge during the treatment than before it; patients treated with placebo were more reactive (P less than 0.05) 14 days after the initiation of treatment. The difference in responsiveness to treatment between the placebo and the cimetidine groups was significant 14 days (P less than 0.01) and 4 weeks (P less than 0.05) after the initiation of treatment; no significant difference in allergen responsiveness was recorded between the groups 1 month after cessation of treatment. No clear-cut changes in specific IgE antibody or total IgE levels, histamine release capacity, or mitogen-induced lymphocyte responsiveness were observed in either group, except that lymphocytes from cimetidine-treated patients tended to show an increased ratio of PHA- to PMA-induced thymidine incorporation. Thus, it was found that the treatment of asymptomatic atopic asthmatics with low-dose cimetidine reduced their allergen sensitivity in bronchial provocation tests by a mechanism which remains to be elucidated.     

豚鼠对蚊虫刺叮的皮肤过敏反应

本文报道在实验室控制条件下,豚鼠经白纹伊蚊连续刺叮3个月内局部皮肤反应的表现和组织病理学的动态变化。结果表明,蚊虫刺叮可引起局部皮肤嗜碱性粒细胞过敏反应,在吸血双翅目昆虫刺叮反应的研究中,尚未见此种报道。     

Specific effects of denaturation, hydrolysis and exposure to Lactococcus lactis on bovine β-lactoglobulin transepithelial transport, antigenicity and allergenicity

BACKGROUND: Food allergy in developed countries represents a growing concern as reflected by epidemiological studies, indicating that up to 4% of the overall population is affected. Reduction of symptoms takes place following eviction or processing of some allergens. However, it cannot be predicted which structural changes will be associated with significant effects on the allergenicity. OBJECTIVE: To determine how various treatments of bovine beta-lactoglobulin (BLG) used as a model antigen alters its immunoreactivity and transepithelial transport, and whether this correlates with reduced allergenicity using an in vitro basophil activation assay. METHODS: BLG was subjected to reduction/alkylation, trypsin digestion or exposed to Lactococcus lactis. The remaining immunoreactivity toward IgG raised against native BLG was assessed by ELISA. Transepithelial transport of BLG and derivatives was examined using polarized Caco-2 cell monolayers mimicking the intestinal epithelium. Selective passage of tryptic peptides was determined using colchicine and cytochalasin D. Basophil activation was measured following stimulation with BLG and derivatives. RESULTS: Reduction/alkylation, trypsin digestion or incubation with L. lactis was associated with decreased BLG recognition by IgG antibodies raised against the native protein. All treatments also resulted in a more efficient transepithelial transport of BLG. BLG crossed the Caco-2 monolayer through passage across the cell, whereas tryptic peptides followed both the para- and transcellular routes. With the exception of denaturation by reduction/alkylation, cross-linking of IgE antibodies by BLG derivatives led to lower basophil degranulation. CONCLUSION: In vitro dissection of antigenicity and allergenicity may be a valid and convenient alternative to evaluate the effects of biotechnological processing on dietary proteins. In addition, it can help to define the molecular and cellular mechanisms that will provide improved means of diagnosis and possibly therapy of food-allergic disorders.     

宿主被硬蜱叮咬后外周血嗜碱粒细胞的变化

在实验室控制条件下，家兔被二棘血蜱分三批进行叮咬、每次间隔１～２周。结果表明，初次叮咬后第二天外周血液嗜碱性粒细胞开始升高，第四天达高峰；再次重复叮咬，嗜碱性粒细胞较初次叮咬仍有显著升高（Ｐ＜０．０１），但升高的时间、方式与初次叮咬略有不同。本文就该现象进行了初步讨论。     

Influence of Bacterial Endotoxins on Basophil Histamine Release Potentiation of Antigen- and Bacteria-Induced Histamine Release

The histamine-releasing capability of lipopolysaccharides (LPS) was examined in human leukocyte suspensions. LPS alone did not release histamine, but was found to enhance the histamine release caused by anti-IgE. Also the IgE-mediated histamine release caused by specific antigens (allergens or bacteria) in sensitized individuals was enhanced by LPS. The potentiating effect of LPS was observed in grass pollen and dog dander allergic patients as well as in patients sensitized to E. coli or Staph. aureus bacteria. No potentiation was obtained by exposure to unspecific allergens or bacteria to which the persons were not sensitized. Bacteria can release histamine by immunological or nonimmunological mechanisms, and only the immunological histamine release was found to be potentiated by LPS. It is speculated that endotoxins reinforce release of histamine caused by allergens in allergic patients or by bacteria in persons sensitized to these microorganisms.     

In vitro expansion of human basophils by interleukin-3 from granulocyte colony-stimulating factor-mobilized peripheral blood stem cells

BACKGROUND: A number of studies support the belief that human basophils play an important role in allergic inflammation. The exact mechanism of basophil activation at the site of allergic inflammation, however, has not been well understood, mainly due to their low number in blood and difficulty in obtaining a sufficient number of highly purified basophils for investigation. OBJECTIVE: The purpose of this study is to expand human basophils in vitro with high yield and purity by culturing peripheral blood stem cells (PBSCs). METHODS: We collected PBSC-rich mononuclear cells containing CD34+ cells (0.15-4.9%) by leukapheresis from patients with malignant lymphoma and lung cancer during haematopoietic recovery after chemotherapy plus granulocyte colony-stimulating factor-induced mobilization. PBSC-rich mononuclear cells were cultured in the presence of IL-3. RESULTS: When PBSC-rich mononuclear cells containing more than 1% of CD34+ cells were cultured, 20.0-83.3% of the cells, mostly with a yield of >10%, were metachromatic cells after 3 weeks of culture. These cells resembled mature peripheral blood basophils morphologically when examined by light and electron microscopy. Flow cytometric analysis showed that they expressed both FcepsilonRI and FcgammaRII. FcepsilonRI cross-linking resulted in intracellular calcium mobilization, histamine release and synthesis of cysteinyl leukotrienes. The intracellular histamine content and the release of these chemical mediators triggered by anti-IgE antibodies were comparable to those of peripheral blood basophils. CONCLUSION: These findings suggest that PBSC-derived basophils expanded in vitro are morphologically and functionally mature and will be a useful tool for the analysis of basophil functions.     

变应性鼻炎的鼻痒发病机制初探

鼻痒作为变应性鼻炎（AR）的主要症状之一严重困扰患者的生活,但目前仍没有完全根治鼻痒的治疗方法,因此,明确AR鼻痒发病机制尤为重要。近年来,AR的神经免疫机制引起许多学者的关注,其中瞬时感受器电位香草酸受体1型（TRPV1）是神经免疫机制的核心要素,在AR鼻痒的发病机制中发挥着重要的桥梁作用。该文综合近年来瘙痒生理病理学机制的研究进展,同时聚焦AR鼻痒的神经传导通路,并从与AR鼻痒有关的免疫细胞（肥大细胞和嗜碱性粒细胞）、介质及信号受体、痒感传入神经（三叉神经）,以及基于TRPV1离子通道剖析AR鼻痒的神经-免疫联动调控网络机制等进行综述,期望为AR鼻痒的临床治疗提供系统的理论依据。     

Proliferation of adenohypophyseal cells into posterior lobe

Summary Proliferation of pituitary basophil cells and occasional chromophobe and eosinophil cells into the posterior lobe was found in 61.8±6.9% (=0.05) in routine necropsy series. The incidence and intensity of proliferation increased in accordance with increasing age. There were no sex differences. The cells were for the most part ACTH-productive; only a few were found to produce somatotropic hormone (STH) or prolactin in exceptional cases, when examined immunocytochemically. Proliferation of these cells appears to take place postnatally, probably in young adult ages. Basophil proliferation, stemming from the pars intermedia, was not related to any clinical features. However, in 6 out of 191 examined cases (3.1±2.5%), the proliferating cells displayed neoplastic potentiality, demonstrated as a combination of mitoses, multinuclear cells, polymorphism, and hypertrophy of the protoplasma in addition to intense proliferation. This finding, described for the first time, may contribute to a better understanding of the origin of silent corticotrophic cell adenomas.This paper is a part of a doctoral thesis (S.K.) at the University of Goettingen, Federal Republic of Germany.