Stem cell factor induces eosinophil activation and degranulation: mediator release and gene array analysis

Oliveira, Sandra Helena Penha de; Taub, Dennis D.; Nagel, James; Smith, Robert E.; Hogaboam, Cory M.; Berlin, Aaron A.; Lukacs, Nicholas W.

doi:10.1182/blood.v100.13.4291

Cited by 68 publications

(63 citation statements)

References 51 publications

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“…To this end, we assessed the level of eosinophil peroxidase in supernatants of 4-hour cultures as previously performed. 4 The eosinophil peroxidase assay demonstrated that a significant degranulation event occurred equally as well when eosinophils were incubated with fibroblasts either from nonallergic mice or from mice that had received chronic allergen exposures ( Figure 3C). When anti-SCF antibody was added to the co-culture, there was a slight but insignificant reduction in the amount of eosinophil peroxidase released into the culture supernatant.…”

Section: Figurementioning

confidence: 90%

“…4 In particular, CCL6 can be produced at significant levels by eosinophils, whereas CCL5 levels are more modest but significantly increased. When the two populations were combined, a significant increase in both CCL5 and CCL6 could be observed in the production of both chemokines (Figure 2, A and B).…”

Section: Ccl5 and Ccl6 Production Requires Contact Between Fibroblastmentioning

confidence: 99%

“…2 Eosinophils have been shown to highly express c-kit (SCF receptor) on their surface. 3,4 We have previously shown that SCF is an important eosinophil-activating factor 4 that influences eosinophil recruitment in allergic airway inflammation. 5 SCF-induced activation of eosinophils has been shown to up-regulate expression of fibroblast growth factors, such as FGF5 and FGF7 (KGF).…”

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confidence: 99%

“…5 SCF-induced activation of eosinophils has been shown to up-regulate expression of fibroblast growth factors, such as FGF5 and FGF7 (KGF). 4 Eosinophils also express at least two potent mediators [interleukin (IL)-1␤ and transforming growth factor (TGF)-␤] that induce a myofibroblast phenotype. The emerging role for the eosinophil in airway remodeling might be important in future anti-asthma strategies.…”

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confidence: 99%

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Eosinophil Activation of Fibroblasts from Chronic Allergen-Induced Disease Utilizes Stem Cell Factor for Phenotypic Changes

Dolgachev

Berlin

Lukacs

2008

The American Journal of Pathology

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In the present studies the role of stem cell factor (SCF) in mediating eosinophil and fibroblast activation during their interaction was investigated. SCF was significantly higher in fibroblasts grown from lungs of chronic allergen-challenged mice compared to fibroblasts grown from normal mice. When eosinophils were layered onto fibroblasts from allergic mice, a significant increase in SCF was detected compared to fibroblasts from nonallergic mice. The interaction of fibroblasts with eosinophils also increased the production of asthmaassociated chemokines, CCL5 and CCL6, was dependent on cell-to-cell interaction, and was observed only with fibroblasts derived from lungs of chronic allergen-challenged mice and not from those derived from unchallenged normal mice. Chemokine production was significantly decreased when anti-SCF antibodies were added during eosinophil-fibroblast interaction. The interaction of fibroblasts from chronic allergen-challenged mice with eosinophils also increased ␣-smooth muscle cell actin and procollagen I expression as well as induced transforming growth factor-␤. The changes in myofibroblast activation were dependent on SCF-mediated pathways because anti-SCF antibody treatment reduced the expression of all three of these latter fibrosisassociated markers. Thus , our data suggest that SCF mediates an important activation pathway for fibroblasts during chronic allergic responses on interaction with recruited eosinophils and suggest a potential mechanism of airway remodeling during chronic disease. Allergic airway inflammation is characterized by peribronchial eosinophil accumulation accompanied by mucus production and airway changes. Structural changes in the asthmatic airway include an increase in smooth muscle mass and deposition of extracellular matrix proteins. These changes correlate with airway hyperresponsiveness, reduced lung function, and an increase in fibroblast and myofibroblast numbers. These debilitating effects are not specifically targeted by current therapeutic agents, presenting a clinical challenge that might be better addressed by an enhanced understanding of the mechanisms. 1 In addition to contributing to airway remodeling, lung fibroblasts may also play a role in local regulation of immune and inflammatory responses. Fibroblasts are a potential source of granulocyte monocyte-colony stimulating factor (GM-CSF) and stem cell factor (SCF), known to promote differentiation, activation, and survival of eosinophils and mast cells. 2 Eosinophils have been shown to highly express c-kit (SCF receptor) on their surface. 3,4 We have previously shown that SCF is an important eosinophil-activating factor 4 that influences eosinophil recruitment in allergic airway inflammation. 5 SCF-induced activation of eosinophils has been shown to up-regulate expression of fibroblast growth factors, such as FGF5 and FGF7 (KGF). 4 Eosinophils also express at least two potent mediators [interleukin (IL)-1␤ and transforming growth factor (TGF)-␤] that induce a myofibroblast phenotype. The emergi...

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Section: Figurementioning

confidence: 90%

Section: Ccl5 and Ccl6 Production Requires Contact Between Fibroblastmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Eosinophil Activation of Fibroblasts from Chronic Allergen-Induced Disease Utilizes Stem Cell Factor for Phenotypic Changes

Dolgachev

Berlin

Lukacs

2008

The American Journal of Pathology

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“…Probably, most of the c-Kit positive cells in the peripheral zone is expressed by eosinophil lineage, in eosinopoiesis foci. Eosinophils have significant levels of surface c-Kit protein, which correspond to stem cell factor receptor (Oliveira et al 2002). There are in vitro evidences that granulocytemacrophage colony stimulating factor (GM-CSF) is a major mediator in increasing granuloma reaction in human schistosomiasis (Rezende et al 2004).…”

Section: Discussionmentioning

confidence: 99%