Effects of interleukin (IL)-3 and IL-5 on human eosinophil degranulation induced by complement components C3a and C5a

Takafuji, Shigeru; Tadokoro, Kenji; Itō, Kōji

doi:10.1111/j.1398-9995.1996.tb00113.x

Cited by 13 publications

(17 citation statements)

References 23 publications

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“…IL-5 and GM-CSF are members of the same hemopoietic cytokine family by sharing a common receptor chain, the ␤-chain, which is thought to be the signal transducer part of the receptor complex (19). IL-5 and GM-CSF have been reported to directly induce degranulation of eosinophil-derived neurotoxin, another eosinophilspecific basic protein, in vitro in human eosinophils (20), while these cytokines only have been shown to act as enhancers on the stimulation-induced ECP degranulation (21). Here it was shown that the hemopoietic cytokines indeed can function as secretagogues for ECP on their own, but contrary to secretion induced by serum-opsonized particles, the cytokine-induced secretion was unaffected by in vivo priming of the eosinophils.…”

Section: Discussionmentioning

confidence: 99%

Eosinophil Cationic Protein (ECP) Is Processed during Secretion

Woschnagg

Rubin

Venge

2009

The Journal of Immunology

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The eosinophil granulocyte is an inflammatory cell involved in allergic diseases such as asthma and rhinitis. Eosinophil cationic protein (ECP) is a basic and potentially cytotoxic granule protein that is released from the eosinophil upon activation. The aim was to study secretion of molecular variants of ECP from blood eosinophils with the hypothesis that the stored noncytotoxic ECP is altered into cytotoxic species upon release from the cell. Eosinophil granulocytes were purified to >95% from venous blood from birch pollen allergic subjects, with symptoms of rhinitis, and from healthy control subjects during the birch pollen season. The cells were stimulated with IL-5, GM-CSF, or serum-opsonized Sephadex particles. Concentration of ECP in cells or supernatants was measured by means of a fluoroenzyme immunoassay, and ECP heterogeneity was studied using an affinity capture assay with the surface-enhanced laser desorption/ionization-time of flight mass spectrometry technique. Extracts of unstimulated eosinophils contained 10 major ECP variants, with molecular masses ranging from 16.1 to 17.7 kDa. Stimulation with particles mainly induced the secretion of two molecular variants at 16.1 and 16.3 kDa, while cytokine stimulation gave rise to a different secretion profile. ECP variants in the pellet extracts remained unaffected by cell activation. The modifications of secreted ECP were partly explained by differences in N-linked glycosylations. Secretion of ECP from eosinophils involves protein modification. The molecular masses of released ECP have acquired the masses of the cytotoxic species.

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Section: Discussionmentioning

confidence: 99%

Eosinophil Cationic Protein (ECP) Is Processed during Secretion

Woschnagg

Rubin

Venge

2009

The Journal of Immunology

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“…Basophils (Kretzschmar et al , 1993) and mast cells (el Lati et al , 1994) react upon AT stimulation with release of histamine. In eosinophils, C3a and C5a regulate the production of eosinophil cationic protein, their adhesion to endothelial cells as well as their migration (Takafuji et al , 1996;DiScipio et al , 1999). C3a further promotes serotonin release from guinea pig platelets (Fukuoka and Hugli, 1988) and modulates synthesis of IL-6 and TNF-α from B cells and monocytes (Fischer and Hugli, 1997;Fischer et al , 1999).…”

Section: Anaphylatoxinsmentioning

confidence: 99%

The role of the anaphylatoxins in health and disease

Klos

Tenner

Johswich

et al. 2009

Molecular Immunology

609

588

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The anaphylatoxins (AT) C3a, C5a and C5a-desArg are generally considered pro-inflammatory polypeptides generated after proteolytic cleavage of C3 and C5 in response to complement activation. Their well appreciated effector functions include chemotaxis and activation of granulocytes, mast cells and macrophages. Recent evidence suggests that ATs are also generated locally within tissues by pathogen-, cell-, or contact system-derived proteases. This local generation of ATs is important for their pleiotropic biologic effects beyond inflammation. The ATs exert most of the biologic activities through ligation of three cognate receptors, i.e. the C3a receptor, the C5a receptor and the C5a receptor-like, C5L2. Here, we will discuss recent findings suggesting that ATs regulate cell apoptosis, lipid metabolism as well as innate and adaptive immune responses through their impact on antigen-presenting cells and T cells. As we will outline, such regulatory functions of ATs and their receptors play important roles in the pathogenesis of allergy, autoimmunity, neurodegenerative diseases, cancer and infections with intracellular pathogens.

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“…We used RPMI 1640 supplemented with 10% FBS and stimulated for 45 min, a condition where adhesion of eosinophils does unlikely occur. Takafuji et al (27) used cytochalasin B in in vitro eosinophil degranulation experiments. Our system did not require cytochalasin B pretreatment.…”

Section: Discussionmentioning

confidence: 99%

Eosinophils Maintain Their Capacity to Signal and Release Eosinophil Cationic Protein Upon Repetitive Stimulation with the Same Agonist

Simon

Weber

Becker

et al. 2000

The Journal of Immunology

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Eosinophils contain in their granules eosinophil cationic protein (ECP) and other basic proteins that have been implicated in immunity to parasites and pathophysiology of chronic allergic responses. In a model of eosinophil degranulation, we show that eosinophils release ECP upon short-term GM-CSF priming and stimulation with either platelet-activating factor (PAF) or the anaphylatoxin C5a, but not eotaxin. Restimulation with the same agonist (PAF or C5a) was unsuccessful as assessed by monitoring intracellular calcium concentration and ECP release. In contrast, upon an intermediate washing step, eosinophils rapidly transduced PAF and C5a signals followed by significant ECP releases. Ligand-binding studies demonstrated that only a proportion of PAF receptors is internalized upon cell stimulation and that washing of the cells removes the agonist from the cell surface. Upon repetitive stimulation, eosinophils with less than 50% of the original ECP content were obtained. Such eosinophils did not increase cellular ECP levels even in the presence of the eosinophil survival factor GM-CSF in overnight cultures. In vivo studies revealed that eosinophils always express detectable amounts of ECP under chronic inflammatory conditions. In conclusion, we have shown that eosinophils maintain their capacity to degranulate upon repetitive stimulation with the same agonist as long as the receptor is not occupied from a previous stimulation. The cellular content of ECP appears to be a no limiting factor in the case of repetitive stimulation, implying that mature eosinophils may not require a significant ECP resynthesis.

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Effects of interleukin (IL)-3 and IL-5 on human eosinophil degranulation induced by complement components C3a and C5a

Cited by 13 publications

References 23 publications

Eosinophil Cationic Protein (ECP) Is Processed during Secretion

Eosinophil Cationic Protein (ECP) Is Processed during Secretion

The role of the anaphylatoxins in health and disease

Eosinophils Maintain Their Capacity to Signal and Release Eosinophil Cationic Protein Upon Repetitive Stimulation with the Same Agonist

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