Human peripheral blood eosinophils express stem cell factor

Hartman, Mor-Li; Piliponsky, Adrian M.; Temkin, Vladislav; Levi‐Schaffer, Francesca

doi:10.1182/blood.v97.4.1086

Cited by 68 publications

(44 citation statements)

References 45 publications

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“…[42][43][44][45][46][47][48] We have previously demonstrated the use of imatinib in our short-term single-challenge model to prevent allergen-induced AHR and reduce inflammation. 49 The present data further support the possibility of using compounds such as imatinib for chronic asthma and inhibiting the remodeling effects of allergic responses. These results are striking.…”

Section: Anti-scf Attenuates Chronic Allergen Responsessupporting

confidence: 60%

Inhibition of SCF attenuates peribronchial remodeling in chronic cockroach allergen-induced asthma

Berlin

Hogaboam

Lukacs

2006

Laboratory Investigation

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The progression and severity of chronic asthma likely depends upon the intensity of the damage and remodeling of the tissue. We have developed a chronic model of allergic asthma using multiple cockroach allergen challenges. Using this clinically relevant allergen we have established significant peribronchial fibrosis and mucus overproduction. These remodeling events are accompanied by intense peribronchial inflammation, including lymphocytes and eosinophils. A cytokine that has been identified as having a prominent role in shortterm allergic events, stem cell factor (SCF), appears to have a significant role in this late-stage process. Using our polyclonal antibody specific for SCF administered into the airways of mice during the final allergen challenges, we find a significant effect on the chronic peribronchial allergen-induced fibrotic remodeling. This was characterized by reduced inflammation, especially eosinophils, as well as reduced hydroxyproline levels in anti-SCF compared to control antibody-treated animals. In addition, when we examined chemokines associated with the chronic disease and neutralized SCF in vivo we observed a corresponding decrease in CCL6 and CCL17. Using an inhibitor, imatinib mesylate, that blocks SCF/c-kit-associated RTK, we find similar results as with anti-SCF for attenuating AHR and fibrotic changes, suggesting that a potential clinical treatment for chronic asthma already exists related to this pathway. These results further support the potential use of SCF/c-kit inhibition for targeting chronic severe asthmatic responses.

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Section: Anti-scf Attenuates Chronic Allergen Responsessupporting

confidence: 60%

Inhibition of SCF attenuates peribronchial remodeling in chronic cockroach allergen-induced asthma

Berlin

Hogaboam

Lukacs

2006

Laboratory Investigation

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“…In fact, it contains mostly ␤-tryptase and only traces of, if any, chymase (29). In addition, HMC-1, like rat peritoneal mast cells, contains other mediators, such as preformed histamine and heparin, TNF-␣, and SCF (29,32,34).…”

Section: Discussionmentioning

confidence: 99%

“…These mediators comprised histamine, TNF-␣, stem cell factor (SCF), and tryptase, all HMC-1 preformed mediators (29,32,34), and IFN-␥, which was recently found to be present in the HMC-1 sonicate (94 pg/ml/1 ϫ 10 6 cells; V. Temkin and F. Levi-Schaffer, unpublished data).…”

Section: Characterization Of the Mast Cell Mediator(s) That Induces Imentioning

confidence: 99%

“…Protein isolation, electrophoresis, and blotting using specific anti-active Abs (for c-Jun N-terminal kinase (JNK), p38, and extracellular signalregulated kinase (ERK)1/2; Promega) were performed essentially as described (32). Lysis buffer (50 mM Tris, 25 mM KCl, 5 mM MgCl 2 , 1 mM EGTA, 1 mM Na 3 VO 4 ) containing a protease inhibitor mixture (SigmaAldrich) was added to cell pellets obtained from 8 -10 ϫ 10 6 of eosinophils.…”

Section: Western Blot Analysis and Emsamentioning

confidence: 99%

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Tryptase Activates the Mitogen-Activated Protein Kinase/Activator Protein-1 Pathway in Human Peripheral Blood Eosinophils, Causing Cytokine Production and Release

Temkin¹,

Kantor²,

Weg³

et al. 2002

The Journal of Immunology

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114

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We have previously shown that mast cells enhance eosinophil survival and activation. In this study we further characterized mast cell activity toward eosinophils. Sonicate of both rat peritoneal mast cells and the human mast cell line 1 (HMC-1) induced a concentration-dependent IL-6 and IL-8 release from human peripheral blood eosinophils (ELISA). HMC-1-induced IL-8 release was significantly reduced by the tryptase inhibitors GW-45 and GW-58 (90 and 87%, respectively, at an optimal concentration) but not by anti-stem cell factor, anti-TNF-α, or anti-IFN-γ neutralizing Abs or by the antihistamine drugs pyrilamine and cimetidine. In a manner similar to HMC-1, human recombinant tryptase induced the expression of mRNA for IL-8 (RT-PCR) and caused IL-8 release from the eosinophils. Addition of cycloheximide, actinomycin D, dexamethasone, PD 98059, curcumin, or SB 202190 completely inhibited the tryptase-induced IL-6 and IL-8 release. In contrast, cyclosporin A had no effect on tryptase-induced IL-8 release. Tryptase caused phosphorylation of extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinases 1 and 2, and p38 (Western blot). Tryptase also induced the translocation of c-Jun from the cytosol to the nucleus (confocal microscopy) and enhanced AP-1 binding activity to the DNA (EMSA). Eosinophils were found to express proteinase-activated receptor 2 (FACS). When eosinophils were incubated with tryptase in the presence of anti-proteinase-activated receptor 2 antagonist Abs a significant decrease in the IL-6 and IL-8 release occurred. In summary, we have demonstrated that the preformed mast cell mediator tryptase induces cytokine production and release in human peripheral blood eosinophils by the mitogen-activated protein kinase/AP-1 pathway.

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“…Within the context of in vivo bone marrow, these cytokines are undoubtedly locally concentrated, and their concerted activities clearly support HSC survival and proliferation. SCF, which is expressed constitutively in BM stromal ®broblasts and endothelial cells, is clearly essential to the survival, proliferation, adhesion/migration and di erentiation of HSC (Broudy, 1997;Hartman et al, 2001). Absence of SCF protein or its receptor C-kit, as displayed in Sl mutation and W mutation respectively, leads to severe macrocytic anemia.…”

Section: Regulation Of Hsc DI Erentiation By the Cytokine Networkmentioning

confidence: 99%

Hematopoietic cytokines, transcription factors and lineage commitment

2002

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The past two decades have witnessed signi®cant advances in our understanding of the cellular physiology and molecular regulation of hematopoiesis. At the heart of stem cell self-renewal and lineage commitment decisions lies the relative expression levels of lineage-speci®c transcription factors. The expression of these transcription factors in early stem cells may be promiscuous and uctuate, but ultimately comes under the in¯uence of extracellular regulatory signals in the form of hematopoietic cytokines. In this review, we ®rst summarize our current understanding of the phenotypic characterization of hematopoietic stem cells. Next, we describe key known transcription factors which govern stem cell selfrenewal and lineage commitment decisions. Finally, we review data concerning the role of speci®c cytokines in in¯uencing these decisions. From this review, a picture emerges in which stem cell fate decisions are governed by the integrated e ects of intrinsic transcription factors and external signaling pathways initiated by regulatory cytokines.

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Human peripheral blood eosinophils express stem cell factor

Cited by 68 publications

References 45 publications

Inhibition of SCF attenuates peribronchial remodeling in chronic cockroach allergen-induced asthma

Inhibition of SCF attenuates peribronchial remodeling in chronic cockroach allergen-induced asthma

Tryptase Activates the Mitogen-Activated Protein Kinase/Activator Protein-1 Pathway in Human Peripheral Blood Eosinophils, Causing Cytokine Production and Release

Hematopoietic cytokines, transcription factors and lineage commitment

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