Transforming growth factor beta abrogates the effects of hematopoietins on eosinophils and induces their apoptosis.

Alam, Rafeul; Forsythe, P.; Stafford, Susan; Fukuda, Yoshiaki

doi:10.1084/jem.179.3.1041

Cited by 141 publications

(86 citation statements)

References 28 publications

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“…Under some conditions, TGF-b may also promote neutrophil oxidant production (Brandes et al 1991;Balazovich et al 1996). Alternatively, TGF-b can act as a negative regulator of granulocytes, and inhibits the survival of human eosinophils by promoting apoptosis and inhibiting cytokine production (Alam et al 1994). Despite these observations, the extent to which TGF-b regulates the granulocytic arm of the innate immune system remains poorly understood.…”

Section: Granulocytesmentioning

confidence: 97%

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Sanjabi

2017

Cold Spring Harb Perspect Biol

452

306

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Transforming growth factor b (TGF-b) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-b alters immunity under various conditions. Under steady-state conditions, TGF-b regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-b inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral ( p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges. Similarly, TGF-b controls the proliferation, survival, activation, and differentiation of B cells, as well as the development and functions of innate cells, including natural killer (NK) cells, macrophages, dendritic cells, and granulocytes. Collectively, TGF-b plays a pivotal role in maintaining peripheral tolerance against self-and innocuous antigens, such as food, commensal bacteria, and fetal alloantigens, and in controlling immune responses to pathogens.

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Section: Granulocytesmentioning

confidence: 97%

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Sanjabi

2017

Cold Spring Harb Perspect Biol

452

306

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“…While TGFb actually suppresses apoptosis in immature CD4 positive lymphocytes (Swain, 1995), in mature cells of the T-lineage (as represented by T-cell lines) TGFb can directly induce apoptosis (Weller et al, 1994). In general however, the action of TGFb on inflammatory cells including haemopoietic progenitors (Jacobsen et al, 1995) mast cells (Mekori and Metcalfe, 1994;Mekori et al, 1995) and eosinophils (Alam et al, 1994) is to abrogate the effect of survival stimuli. Thus, in the anterior chamber of the eye where high levels of active TGFb2 are found (Granstein et al, 1990), TGFb will presumably hasten the demise of any inflammatory cell present and aid in the suppression of a potentially damaging response.…”

Section: Programmed Cell Death In Ocular Immune Privilegementioning

confidence: 99%

Apoptosis in mammalian eye development: lens morphogenesis, vascular regression and immune privilege

Lang

1997

Cell Death Differ

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Formation of the mammalian eye requires a complex series of tissue interactions that result in an organ of exquisite sensory capability. The early steps in eye development involve extensive cell death associated with morphogenesis. Later, suppression of programmed cell death is essential for tissue differentiation and in the adult, the immune privileged status of the eye is maintained in part through factors that induce inflammatory cell apoptosis. Experimental evidence suggests that suppression of apoptosis in cells of the lens lineage by fibroblast growth factors is one component of their action during lens morphogenesis. Fibroblast growth factors are also required for normal lens fiber-cell differentiation. This includes a degenerative step for organelles that is presumably an adaptation for the clearance of light scattering elements from the optic axis. The process of organelle degeneration may be related to apoptosis in a few of its features. Activelyinduced apoptosis becomes important for eye development as the temporary ocular vasculatures regress. This too, is presumably an adaptation for the disposal of cells that would disturb the passage of light to the retina. Ocular macrophages appear to be essential for the induction of apoptosis in the endothelial cells comprising the ocular vasculatures. In the adult, inflammatory cells entering the eye are exposed to the pro-apoptotic agents transforming growth factor-b2 and Fas ligand. The expression of these molecules in the eye, and their action in killing inflammatory cells, has evolved as a means of preventing inflammation and subsequent loss of vision. Thus, the eye offers a unique and versatile system for studying the role of programmed cell death in lens development, vascular regression and immune privilege.

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“…When mature peripheral blood eosinophils are cultured in the absence of these cytokines, they undergo apoptosis (10), because eosinophils at least in part substantially lack the expression of Bcl-2, an antiapoptotic protein (11). Not only deprivation of eosinophil-activating cytokines, but also some cytokines, such as IL-4 (12) and TGF-␤ (13), or ligation of cell surface molecules, including Fas (CD95) (14) and CD69 (15), are capable of inducing apoptosis in human eosinophils. Administration of mAbs against IL-5 (16), or against Fas (17) are reported to be of potent therapeutic value in animal models of allergic asthma.…”

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confidence: 99%

Extremely Rapid and Intense Induction of Apoptosis in Human Eosinophils by Anti-CD30 Antibody Treatment In Vitro

Matsumoto

Terakawa

Miura

et al. 2004

The Journal of Immunology

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Apoptosis is an important cellular mechanism for controlling cell viability and proliferation. With respect to eosinophils, cytokines prolong their survival, whereas corticosteroids reduce their survival in vitro. CD30, a member of the TNFR family, is expressed on the surface of many cell types, including Hodgkin’s lymphoma cells. CD30 is capable of inducing apoptosis after Ab treatment in some cell lines. To determine whether this surface structure is involved in apoptosis of human eosinophils, we examined its expression and the effect of anti-CD30 Ab treatment on the viability of eosinophils. Purified human eosinophils expressed low, but consistently detectable, levels of CD30. Immobilized, but not soluble, forms of anti-CD30 Abs (HRS-4 and Ber-H8) or recombinant mouse CD30 ligand exhibited an extremely rapid and intense survival-reducing effect on the eosinophils in the presence of exogenous IL-5; this effect was both concentration and time dependent. Furthermore, high concentrations of IL-5 could not reverse the reduced survival rates. After treatment with anti-CD30 Ab, gel electrophoresis of DNA extracted from the eosinophils demonstrated changes consistent with apoptosis. The immobilized F(ab′)2 of the anti-CD30 Ab failed to induce eosinophil apoptosis. The addition of anti-CD18 Ab also completely abrogated the induction of eosinophil apoptosis. Further examination using specific signal transduction inhibitors suggested the involvement of p38, mitogen-activated protein kinase kinase 1/2, and specific tyrosine kinase, but not NF-κB, in the induction of CD30-mediated eosinophil apoptosis. These data demonstrate that CD30 can modify eosinophil survival by causing an extremely rapid and intense induction of apoptosis through a tightly regulated intracellular signaling pathway.

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Transforming growth factor beta abrogates the effects of hematopoietins on eosinophils and induces their apoptosis.

Cited by 141 publications

References 28 publications

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Apoptosis in mammalian eye development: lens morphogenesis, vascular regression and immune privilege

Extremely Rapid and Intense Induction of Apoptosis in Human Eosinophils by Anti-CD30 Antibody Treatment In Vitro

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