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Biomedical subjects

B F Gibbs

Publications and source records attributed to B F Gibbs.

At least 19 recordsLinked to original sources
PubMed2005

Human basophils as effectors and immunomodulators of allergic inflammation and innate immunity.

Basophils have often stood in the shadow of their tissue-fixed mast cell counterparts which share some, common features, such as high-affinity IgE receptor expression and the ability to release histamine. That rodent mast cells produce a variety of pro-allergic and inflammatory cytokines has further added to the deception that basophils only play a minor role in allergic inflammation. Surprisingly, in humans, basophils, but not mast cells, appear to be the prime early producers of the Th2-type cytokines IL-4 and IL-13, which perform several crucial functions in initiating and maintaining allergic responses. This putative immunomodulatory role of basophils is supported further by their ability to express CD40 ligand, which, together with IL-4 and IL-13, serve as inductors of B-cell proliferation and class switching to IgE and IgG4. Moreover, human basophils are the main cellular source for rapid IL-4 generation, a mandatory requirement for the development of Th2 responses. Recent specific staining techniques have localised basophils in various tissues affected by allergic diseases and it appears likely, but remains to be proven, that the interaction of basophils, T cells and B cells at these sites propagate pro-allergic immune responses. Additionally, basophil activation is not restricted to antigen-specific IgE crosslinking but can be caused in non-sensitised individuals by parasitic antigens, plant lectins and viral superantigens binding to non-specific IgEs. Finally, the presence of novel IgE-independent receptor targets that cause trafficking and Th2 cytokine release from basophils further underlines their potential role in innate as well as adaptive immunity.

Basophils↗
PubMed2004

Echinococcus multilocularis metacestode extract triggers human basophils to release interleukin-4.

Infections with parasitic helminths are associated with a T helper 2 (Th2) immune response and IgE production. The underlying mechanism, however, is only partially understood. Recently we have isolated a protein from extracts of Schistosoma mansoni eggs that triggers human basophils from non-sensitized donors to release interleukin-4 (IL-4), the key cytokine of a Th2 response. We called this protein IPSE (for IL-4-inducing principle from Schistosoma mansoni eggs). Supposing that IPSE-like IL-4-inducing activities might be a general principle shared among different helminth species, we investigated extracts from the cestode E. multilocularis for its effect on human basophils. Our results showed that extracts from metacestodes of E. multilocularis cause basophil degranulation, as well as the secretion of histamine, IL-4 and IL-13, in a dose-dependent manner. IgE stripping and resensitization of basophils indicated that the mechanism of IL-4 induction requires the presence of IgE on the cells. Since analogous properties have been demonstrated earlier for IPSE, we think that S. mansoni and E. multilocularis may induce a Th2 response in their hosts via a related mechanism, namely, by the induction of IL-4 release from basophils.

Animals↗
PubMed2003

Interleukin-4 production from human basophils is critically dependent on the storage conditions employed prior to stimulation.

OBJECTIVE AND DESIGN: Marked variations in the interleukin-4 (IL-4)-producing capacity of basophils can be observed when aliquots from the same cell preparation are kept under different conditions before stimulation. The aim of this study was to identify factors affecting the functional activity of basophils and to determine optimal storage conditions. SUBJECTS: Healthy blood donors. METHODS: Aliquots of purified basophils were kept for different time intervals on ice or at 37 degrees C, in buffer or culture medium, respectively. Following subsequent stimulation with anti-IgE, IL-4 release was determined. RESULTS: Upon storage times up to 4 h, basophils produced more IL-4 when kept at 37 degrees C as compared to 4 degrees C. Surprisingly, buffer was superior compared to culture medium for storage. When the storage time was 20 h, IL-4 release was reduced significantly under all conditions studied. CONCLUSION: The storage conditions considerably affect basophil IL-4 release and thus should taken into account when comparing results.

Antibodies, Blocking↗
PubMed2003

Calcineurin antagonists differentially affect mediator secretion, p38 mitogen-activated protein kinase and extracellular signal-regulated kinases from immunologically activated human basophils.

BACKGROUND: Basophils participate in allergic diseases by invading affected tissues and secreting histamine, leukotriene (LT)C4, IL-4 and IL-13 following FcepsilonRI cross-linking. A reduction of basophil mediator production is therefore of considerable therapeutical interest. Macrolactam derivatives, which inhibit calcineurin activation, may be candidates for antiallergic therapy as they reduce both symptoms of inflammatory skin disease in animal models and mast cell degranulation. OBJECTIVE: To investigate the effects of the calcineurin antagonists ascomycin and cyclosporin A on IgE-dependent mediator release from human basophils. METHODS: Basophils were purified by Ficoll density centrifugation, elutriation and negative selection. Histamine release was measured spectrofluorometrically; LTC4, IL-4 and IL-13 secretions were assayed by enzyme-linked immunosorbent assay (ELISA). Lysed cells were subjected to Western blotting using specific antibodies to phospho-p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK)-1 and -2. RESULTS: Ascomycin (0.01 nm to 1 micro m) and cyclosporin A (0.1 nm to 10 micro m) strikingly inhibited (maximally 100%) anti-IgE-induced histamine and cytokine release from basophils, and these actions were unaffected by IL-3 priming. Ascomycin, however, was less potent at blocking LTC4 secretion, whereas cyclosporin A was unable to block production of this mediator. In immunoblotting studies, ascomycin and cyclosporin A reduced IgE-dependent p38 MAPK activation but were less potent at reducing ERK phosphorylation in basophils. CONCLUSION: Calcineurin antagonists like ascomycin and cyclosporin A block IgE-dependent basophil degranulation and cytokine synthesis. Calcineurin may target p38 MAPK activation, but seems to have less activity on ERK phosphorylation. This is paralleled by a reduced or even absent effect of calcineurin antagonists on eicosanoid production.

Basophils↗
PubMed2001

Mercuric chloride enhances immunoglobulin E-dependent mediator release from human basophils.

Mercuric chloride (HgCl2) is an industrial agent known to cause autoimmune disorders and induce IgE synthesis, which plays a crucial role in the manifestation of allergic diseases. In rodents, the immunomodulatory effects of HgCl2 have been shown to involve the enhancement of mast cell-derived IL-4 secretion, which facilitates both Th2-lymphocyte development and IgE production. In humans, rapid allergen-dependent release of IL-4 and the related cytokine IL-13 from histamine-containing cells occurs primarily in basophils, along with other proinflammatory mediators such as histamine and LTC4. In this study, we therefore investigated the effects of HgCl2 on the release of the above basophil mediators, either due to the compound alone or in conjunction with IgE-dependent stimulation. HgCl2 (10(-9) to 10(-6) M) did not induce mediator secretion alone but significantly enhanced the release of histamine, LTC4, IL-4, and IL-13 caused by anti-IgE. Higher concentrations of HgCl2 (10(-5) to 10(-3) M) strikingly reduced cell viability; however, toxicity varied depending on cell density and incubation time. Removal of HgCl2 following a short incubation with basophils did not reverse the potentiating effects on basophil mediator secretion to anti-IgE and the concentration of free mercury in the supernatants significantly diminished by up to 20% after incubation with the cells, indicating irreversible Hg binding to cells. By upregulating IgE-dependent human basophil mediator release, our results clearly indicate that HgCl2 potentially exacerbates allergic disorders and promotes a Th2-cytokine profile.

Antibodies, Anti-Idiotypic↗
PubMed2001

Heavy metal removal from sediments by biosurfactants.

Batch washing experiments were used to evaluate the feasibility of using biosurfactants for the removal of heavy metals from sediments. Surfactin from Bacillus subtilis, rhamnolipids from Pseudomonas aeruginosa and sophorolipid from Torulopsis bombicola were evaluated using a metal-contaminated sediment (110mg/kg copper and 3300mg/kg zinc). A single washing with 0.5% rhamnolipid removed 65% of the copper and 18% of the zinc, whereas 4% sophorolipid removed 25% of the copper and 60% of the zinc. Surfactin was less effective, removing 15% of the copper and 6% of the zinc. The technique of ultrafiltration and zeta potential measurements were used to determine the mechanism of metal removal by the surfactants. It was then postulated that metal removal by the biosurfactants occurs through sorption of the surfactant on to the soil surface and complexation with the metal, detachment of the metal from the soil into the soil solution and hence association with surfactant micelles. Sequential extraction procedures were used on the sediment to determine the speciation of the heavy metals before and after surfactant washing. The carbonate and oxide fractions accounted for over 90% of the zinc present in the sediments. The organic fraction constituted over 70% of the copper. Sequential extraction of the sediments after washing with the various surfactants indicated that the biosurfactants, rhamnolipid and surfactin could remove the organically-bound copper and that the sophorolipid could remove the carbonate and oxide-bound zinc. Therefore, heavy metal removal from sediments is feasible and further research will be conducted.

Biodegradation, Environmental↗
PubMed2001

An evaluation of technologies for the heavy metal remediation of dredged sediments.

Sediments dewatering is frequently necessary after dredging to remediate and treat contaminants. Methods include draining of the water in lagoons with or without coagulants and flocculants, or using presses or centrifuges. Treatment methods are similar to those used for soil and include pretreatment, physical separation, thermal processes, biological decontamination, stabilization/solidification and washing. However, compared to soil treatment, few remediation techniques have been commercially used for sediments. In this paper, a review of the methods that have been used and an evaluation of developed and developing technologies is made. Sequential extraction technique can be a useful tool for determining metal speciation before and after washing. Solidification/stabilization techniques are successful but significant monitoring is required, since the solidification process can be reversible. In addition, the presence of organics can reduce treatment efficiency. Vitrification is applicable for sediments but expensive. Only if a useful glass product can be sold will this process be economically viable. Thermal processes are only applicable for removal of volatile metals, such as mercury and costs are high. Biological processes are under development and have the potential to be low cost. Since few low cost metal treatment processes for sediments are available, there exists significant demand for further development. Pretreatment may be one of the methods that can reduce costs by reducing the volumes of sediments that need to be treated.

Biodegradation, Environmental↗
PubMed2001

Do basophils play a role in immunity against parasites?

The link between parasites and eosinophilia has been known for more than a century, although the role of eosinophils in host protection is still an open issue. Much less appreciated, however, is the concurrent systemic induction of a related cell type, the basophil, in parasitized hosts. To date, little is known about the role of basophils in immunity against parasites, but recent evidence points to a possible crucial role in the initiation of T-helper type 2 responses in the host. In this article, we review the current understanding of parasitic infections and basophils and discuss their putative role in immunity.

Animals↗
PubMed2001

Human skin mast cells rapidly release preformed and newly generated TNF-alpha and IL-8 following stimulation with anti-IgE and other secretagogues.

Several groups have previously reported that rodent or human leukemic mast cells produce inflammatory cytokines such as TNF-alpha and IL-8 as well as the pro-allergic cytokines IL-4, IL-5 and IL-13. Comparatively little is known, however, regarding the ability of normal human skin mast cells to secrete these factors following either IgE-dependent or IgE-independent modes of activation. We therefore investigated whether normal human skin mast cells produce these cytokines following stimulation by a variety of secretagogues. Enriched isolated skin mast cells released both TNF-alpha and IL-8 following activation with either anti-IgE, SCF, substance P, compound 48/80 or A23187. This release was dose- and time-dependent, with maximal levels being reached within 4 h of stimulation involving, in part, the secretion of preformed stores of both cytokines. In accordance with this, using lysates of highly purified (>90%) skin mast cells, we could demonstrate that both TNF-alpha and IL-8 mRNA and protein were present in both unstimulated as well as stimulated mast cells. In stark contrast to these results, no significant levels of either IL-4, IL-5 or IL-13 were detected, regardless of the secretagogue used or the period of stimulation. These results show that human skin mast cells are capable of rapidly secreting pro-inflammatory cytokines like TNF-alpha and IL-8 following IgE-dependent activation and stimulation by the neuropeptide substance P, SCF and the basic polypeptide analogue compound 48/80. In contrast to other types of human mast cells however, human skin mast cells were incapable of secreting IL-4, IL-5 or IL-13 in these settings.

Antibodies, Anti-Idiotypic↗