Dietary lectins can inducein vitro release of IL-4 and IL-13 from human basophils

Haas, Helmut; Falcone, Franco H.; Schramm, Gabriele; Haisch, Karin; Gibbs, Bernhard F.; Klaucke, Jens; Pöppelmann, Marco; Becker, Wolf‐Meinhard; Gabius, Hans‐Joachim; Schlaak, M

doi:10.1002/(sici)1521-4141(199903)29:03<918::aid-immu918>3.0.co;2-t

Cited by 87 publications

(15 citation statements)

References 32 publications

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“…The possibility that IPSE acts as a lectin cannot be excluded, but its sequence does not show any similarity with known animal or plant lectins. Furthermore, although several lectins can activate basophils (32), the concentrations required are in the g/ml range. In contrast, the possibility that IPSE is a B cell superantigen requires consideration; B cell superantigens, such as HIV-1 gp120, protein Fv, and protein L (33,34), 2 can bind to IgE and, as multivalent molecules, can activate basophils, resulting in the release of IL-4 and IL-13.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of an Interleukin-4-inducing Factor from Schistosoma mansoni Eggs

Schramm

Falcone

Gronow

et al. 2003

Journal of Biological Chemistry

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173

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The eggs of the parasitic trematode Schistosoma mansoni are powerful inducers of a T helper type 2 (Th2) immune response and immunoglobulin E (IgE) production. S. mansoni egg extract (SmEA) stimulates human basophils to rapidly release large amounts of interleukin (IL)-4, the key promoter of a Th2 response. Here we show purification and sequence of the IL-4-inducing principle of S. mansoni eggs (IPSE). Stimulation studies with human basophils using SmEA fractions and natural and recombinant IPSE as well as neutralization and immunodepletion studies using antibodies to recombinant IPSE demonstrate that IPSE is the bioactive principle in SmEA leading to activation of basophils and to expression of IL-4 and IL-13. Regarding the mechanism of action, blot analysis showed that IPSE is an IgE-binding factor, suggesting that it becomes effective via crosslinking receptor-bound IgE on basophils. Immunohistology revealed that IPSE is enriched in and secreted from the subshell area of the schistosome egg. We conclude from these data that IPSE may be an important parasitederived component for skewing the immune response toward Th2.Infection with the parasitic trematode Schistosoma mansoni leads to a pronounced Th2 1 response and to elevated IgE production both in humans and in experimental animals. The definition of parasite-derived products capable of skewing the immune response toward Th2 would not only enhance our understanding of the defense mechanisms involved in helminth infections but may also lead to new insights into the pathogenesis of immediate-type hypersensitivity diseases such as asthma. However, in contrast to our increasing understanding of how pathogen-derived products can initiate Th1-type immune responses, there is so far little detailed knowledge about the nature of the parasite-derived molecule(s) and the underlying mechanisms that trigger and/or amplify a Th2-type reaction. In S. mansoni infection, a critical role in inducing a polarized Th2 response is played by the egg stage of the parasite (1), since a Th2 response and IgE production are only observed after egg deposition or following injection of schistosome eggs (2) or extracts thereof (3) into naive animals. By contrast, the initial larval (schistosomula) and adult worm stages rather induce a response skewed to Th1.It is now firmly established, both in vivo and in vitro, that the cytokine profile present during an immune reaction is an important element in directing the response to Th1 or Th2 and that IL-4 is the key cytokine responsible for biasing the immune reaction toward a Th2 phenotype (4 -7). In the human system, basophils are a prominent source of IL-4 and IL-13; these cells secrete large amounts of IL-4 and IL-13 in response to IgE-receptor cross-linking or activation by a combination of IL-3 and C5a (8, 9). Indeed, human basophils can be viewed as "innate Th2-type" effector cells, since IL-4 and IL-13 are expressed in a very restricted manner without production of any of the cytokines involved in Th1-type immune responses. We therefore ...

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Section: Discussionmentioning

confidence: 99%

Molecular Characterization of an Interleukin-4-inducing Factor from Schistosoma mansoni Eggs

Schramm

Falcone

Gronow

et al. 2003

Journal of Biological Chemistry

Self Cite

173

192

View full text Add to dashboard Cite

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“…In vitro , it has been demonstrated that incubation with lectin from red kidney bean lead to T cell proliferation and increased cytokine production (7). Haas et al demonstrated that certain dietary lectins can cause IL-4 and IL-13 release from basophils (8), while Gong et al demonstrated that plant lectins can activate NLRP3 inflammasome in macrophages, although at concentrations outside of normal physiological conditions (9). Recently it has been shown that certain lectins can activate toll-like receptors (TLRs) in a distinct, yet comparable, fashion to activation by pathogens.…”

Section: Introductionmentioning

confidence: 99%

Wheat Germ Agglutinin as a Potential Therapeutic Agent for Leukemia

et al. 2019

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Dietary lectins are carbohydrate-binding proteins found in food sources. We used a panel of seven dietary lectins to analyze cytotoxicity against hematological cancers. Wheat germ agglutinin (WGA), even at low doses, demonstrated maximum toxicity toward acute myeloid leukemia (AML) cells. Using AML cell lines, we show time- and dose-dependent killing by WGA. We also show that low doses of WGA kills primary patient AML cells, irrespective of subtype, with no significant toxicity to normal cells. WGA caused AML cell agglutination, but failed to agglutinate RBC's at this dose. WGA, primarily, binds to N -acetyl-D-glucosamine (GlcNAc) and is also reported to interact with sialic-acid-containing glycoconjugates and oligosaccharides. After neuraminidase pre-treatment, which catalyzes the hydrolysis of terminal sialic acid residues, AML cells were less sensitive to WGA-induced cell death. AML cells were also not sensitive to succinyl-WGA, which does not react with sialic acid. Incubation with LEL lectin, which recognizes GlcNAc or SNA, which binds preferentially to sialic acid attached to terminal galactose in α-2,6 and to a lesser degree α-2,3 linkage, did not alter AML cell viability. These data indicate that WGA-induced AML cell death is dependent on both GlcNAc binding and interaction with sialic acids. We did not observe any in vitro or in vivo toxicity of WGA toward normal cells at the concentrations tested. Finally, low doses of WGA injection demonstrated significant in vivo toxicity toward AML cells, using xenograft mouse model. Thus, WGA is a potential candidate for leukemia therapy.

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“…In addition, WGA has an important effect on the immune system, as it can stimulate the immune system inducing the production of pro-inflammatory cytokines both in human peripheral blood mononuclear cells (PBMC) [50,51] and in animals [52,53].…”

Section: Wheat Germ Agglutinin (Wga)mentioning

confidence: 99%

Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders

et al. 2020

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Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut–brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut–brain interaction.

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Dietary lectins can inducein vitro release of IL-4 and IL-13 from human basophils

Cited by 87 publications

References 32 publications

Molecular Characterization of an Interleukin-4-inducing Factor from Schistosoma mansoni Eggs

Molecular Characterization of an Interleukin-4-inducing Factor from Schistosoma mansoni Eggs

Wheat Germ Agglutinin as a Potential Therapeutic Agent for Leukemia

Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders

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