Purified human peripheral blood basophils release interleukin‐13 and preformed interleukin‐4 following immunological activation

Gibbs, Bernhard F.; Haas, Helmut; Falcone, Franco H.; Albrecht, Claudia; Vollrath, I. B.; Noll, Tobias; Wolff, Helmut H.; Amon, Ulrich

doi:10.1002/eji.1830261033

Cited by 155 publications

(121 citation statements)

References 26 publications

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“…Moreover, because basophils have preformed IL-4, these cells can release IL-4 very quickly in response to an appopriate stimulus. Although we have demonstrated that basophils release IL-4 as quickly as 2 h after exposure to BmAg (the shortest time period we evaluated), basophils have been documented to release IL-4 within 5-10 min of IgE cross-linking (13). Also, because basophils can maintain IgE-mediated memory for at least 1 mo even in the absence of ongoing de novo IgE production (29), basophils may be responsible for quickly re-establishing a Th2 response against future filarial exposures in patients who have been infected previously with filariae.…”

Section: Discussionmentioning

confidence: 83%

“…Although this may be a valid finding, it is also possible that the conditions we used were insensitive for the detection of IL-13. In particular, we may have used insufficient duration of cell culture time, as IL-13 release from basophils may not peak until at least 24 h after basophil activation (13).…”

Section: Discussionmentioning

confidence: 99%

“…Of all PBMC, only basophils have the ability to produce IL-4 early in response to a stimulus (12), releasing preformed IL-4 within 5-10 min of IgE surface cross-linking (13). After activation, basophils also synthesize IL-4 and IL-13 de novo, with time-course experiments showing a second peak of IL-4 release after 4 h and a first peak of IL-13 release at 24 h (13). Recently, basophils from filaria-infected patients have been shown to release IL-4 in response to L3 larval and adult filarial Ag (14).…”

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confidence: 99%

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Parasite Antigen-Driven Basophils Are a Major Source of IL-4 in Human Filarial Infections

Mitre

Taylor

Kubofcik

et al. 2004

The Journal of Immunology

101

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Basophil contribution to the IL-4 pool in filarial infections was assessed using PBMC from 20 patients with active filarial infections and from 9 uninfected subjects. Patient basophils released histamine in response to Brugia malayi Ag (BmAg). They also released IL-4 within 2 h after exposure to BmAg, as assessed by intracellular cytokine flow cytometry. This IL-4 induction was Ag specific, as IL-4 was not detected in BmAg-exposed basophils obtained from uninfected subjects. Although there were, on average, 64 times more CD4+ T cells than basophils in the peripheral circulation of filaria-infected patients, the absolute numbers of basophils and CD4+ T cells producing IL-4 per 100,000 PBMC were equivalent (geometric mean: 16 IL-4-producing basophils/100,000 PBMC vs 22 IL-4-producing CD4+ T cells/100,000 PBMC). Basophils also released IL-4 in response to both low and high concentrations of BmAg, whereas CD4+ T cells released IL-4 only after incubation with a high concentration of BmAg, raising the possibility that basophils, due to their lower threshold for activation, may actually release IL-4 more frequently than CD4+ T cells in vivo. Furthermore, IL-4 production in vitro by Ag-stimulated purified basophils or CD4+ T cells provided evidence that basophils release greater quantities of IL-4 per cell than CD4+ T cells in response to BmAg. These results suggest that, when Ag-specific IgE is present in a filaria-infected individual, basophils function to amplify the ongoing Th2 response by releasing IL-4 in greater amounts and possibly more frequently than CD4+ T cells in response to filarial Ag.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Parasite Antigen-Driven Basophils Are a Major Source of IL-4 in Human Filarial Infections

Mitre

Taylor

Kubofcik

et al. 2004

The Journal of Immunology

101

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“…Constitutive IL-4 transcripts, moreover, are potentially required to replenish intracellular stores of preformed IL-4 protein in basophils (Figs. 2C and 8C) (55,56).…”

Section: Discussionmentioning

confidence: 99%

Mast Cells, Basophils, and Eosinophils Acquire Constitutive IL-4 and IL-13 Transcripts during Lineage Differentiation That Are Sufficient for Rapid Cytokine Production

Gessner

Mohrs

2005

The Journal of Immunology

258

243

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Mast cells, basophils, and eosinophils are myeloid cells that are distinguished by their capability to produce IL-4 and IL-13. However, it is not clear how this potential is related to the lineage differentiation of these subsets. In the present study we used bicistronic IL-4 reporter (4get) mice to directly visualize IL-4 expression by nonlymphoid cells in vitro and in vivo at the single-cell level. Our data show that frequent expression of both Il4 alleles is initiated and maintained during ontogeny by an IL-4Rα- or Stat6-independent mechanism. Despite the constitutive presence of cytokine transcripts in differentiated cells under steady state conditions, cytokine production is not detectable in the absence of stimulation. Moreover, mature mast cells, basophils, and eosinophils also constitutively express IL-13. Both preformed IL-4 and IL-13 mRNAs are sufficient for rapid cytokine production upon stimulation. Our data show that mast cells, basophils, and eosinophils are programmed for IL-4 and IL-13 expression early in ontogeny. These novel findings have important implications for the prevention and therapeutic intervention of allergic and asthmatic diseases.

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“…Basophils could enhance Th2-associated immune responses since they release IL-4 within minutes of activation. 11,12 Activation can occur by crosslinking of surface-bound IgE molecules or by a large variety of substances in an antigen-unspecific manner (reviewed in Falcone et al 2 ). Mast cells and basophils express constitutively low levels of IL-4, which can be visualized by using sensitive IL-4 reporter mice expressing enhanced green fluorescent protein (eGFP) under control of regulatory elements of IL-4 (4get mice 13 ).…”

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confidence: 99%

Basophil effector function and homeostasis during helminth infection

Ohnmacht¹,

Voehringer²

2009

Blood

177

161

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IntroductionBasophil development and function is poorly understood, although this rare cell type was identified by Paul Ehrlich in 1879. 1 Basophils constitute less than 0.3% of leukocytes in the peripheral blood. They are functionally closely related to mast cells, since both cell types express the high-affinity receptor for IgE and produce similar effector molecules, including histamine, lipid mediators (eg, leukotrienes and prostaglandins), serine proteases, and interleukins (eg, IL-4, IL-13, and IL-6). 2 However, the developmental and functional relationship of basophils to other cell types is not clearly established. Helminth infections of mice cause a dramatic increase in basophil numbers, which is thought to be mediated by However, naive IL-3-deficient mice have normal levels of basophils, indicating that IL-3 promotes basophil development and/or survival but is not essential for the basophil lineage. 3 Increased numbers of basophils are found in the skin during the late-phase response of contact dermatitis 4 or atopic dermatitis. 5 Basophils are found in the lungs of patients with allergic asthma, and probably contribute to pathogenesis during fatal asthma. 6,7 On the other hand, they might contribute to protective immunity against helminths since basophils are an important source for IL-4 and IL-13. 8 Recently, basophils have been shown to be implicated in polarization of T-helper 2 (Th2) cells by allergens with protease activity 9 and IgG1-mediated anaphylaxis, 10 which further demonstrates their important functions during type 2 immune responses.The turnover of basophils has not yet been described, and their localization in tissues is essentially unknown. Basophils could enhance Th2-associated immune responses since they release IL-4 within minutes of activation. 11,12 Activation can occur by crosslinking of surface-bound IgE molecules or by a large variety of substances in an antigen-unspecific manner (reviewed in Falcone et al 2 ). Mast cells and basophils express constitutively low levels of IL-4, which can be visualized by using sensitive IL-4 reporter mice expressing enhanced green fluorescent protein (eGFP) under control of regulatory elements of IL-4 (4get mice 13 ). Infection of 4get mice with the helminth Nippostrongylus brasiliensis causes massive type 2 immune responses in the lung and small intestine, providing a valuable model to study basophil function during parasitic infections in vivo.Here, we analyzed basophil development and turnover by flow cytometry, BrdU incorporation, and adoptive transfer. We determined the localization of basophils in the spleen, lung, and small intestine of N brasiliensis-infected mice by immunofluorescence staining of tissue sections. Basophils were found to promote differentiation of alternatively activated macrophages in the lung, induce systemic eosinophilia, and contribute to worm expulsion in N brasiliensis-infected mice, demonstrating their central role during the effector phase of a type 2 immune response against helminths. MethodsMice IL-4 reporter ...

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Purified human peripheral blood basophils release interleukin‐13 and preformed interleukin‐4 following immunological activation

Cited by 155 publications

References 26 publications

Parasite Antigen-Driven Basophils Are a Major Source of IL-4 in Human Filarial Infections

Parasite Antigen-Driven Basophils Are a Major Source of IL-4 in Human Filarial Infections

Mast Cells, Basophils, and Eosinophils Acquire Constitutive IL-4 and IL-13 Transcripts during Lineage Differentiation That Are Sufficient for Rapid Cytokine Production

Basophil effector function and homeostasis during helminth infection

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