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Stem cell factor in nasal polyposis and allergic rhinitis: Increased expression by structural cells is suppressed by in vivo topical corticosteroids 

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Presentation on theme: "Stem cell factor in nasal polyposis and allergic rhinitis: Increased expression by structural cells is suppressed by in vivo topical corticosteroids "— Presentation transcript:

1 Stem cell factor in nasal polyposis and allergic rhinitis: Increased expression by structural cells is suppressed by in vivo topical corticosteroids  Young-Ki Kim, MD, Noriaki Nakagawa, MD, Koichi Nakano, MD, Irakly Sulakvelidze, MD, Jerry Dolovich, MD†, Judah Denburg, MD  Journal of Allergy and Clinical Immunology  Volume 100, Issue 3, Pages (September 1997) DOI: /S (97) Copyright © 1997 Mosby, Inc. Terms and Conditions

2 Fig. 1 Northern blot analysis of SCF mRNA expression. Total RNA (10 μg/ml) was hybridized with 32P-radiolabeled SCF probe. RNA of NpFbs stimulated with lipopolysaccharide (lane 2), NpFbs stimulated with IL-1β (lane 3), and unstimulated NpFbs (lane 4) shows 7.5 Kb and 5.5 Kb SCF-specific transcripts. Lanes 1 and 5 (HepG 2 and HeLa cell RNA, respectively) show SCF transcripts. Ribosomal RNA (lane 6) was used as negative control, and RNA from HeLa cells and HepG 2 cells were used as positive controls. LPS, Lipopolysaccharide. Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

3 Fig. 2 SCF production by cultured NpEps and NpFbs, measured by ELISA. The level of SCF in NpEpCM is the mean of duplicate determinations in each of two experiments. The level of SCF in NpFbCM represents the mean of duplicate determinations in each of three experiments. Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

4 Fig. 3 Polyp fibroblast SCF induces mast cell differentiation. Percent stimulation of mast cell differentiation induced by rhSCF (25 ng/ml) (A) and NpFbCM (B). Abrogation by anti-hSCF antibody (αSCF). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

5 Fig. 3 Polyp fibroblast SCF induces mast cell differentiation. Percent stimulation of mast cell differentiation induced by rhSCF (25 ng/ml) (A) and NpFbCM (B). Abrogation by anti-hSCF antibody (αSCF). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

6 Fig. 4 Immunohistochemical localization of SCF in nasal tissues. A, Photomicrograph (×640) demonstrating immunoreactive SCF protein diffusely in cytoplasm of cultured NpEps with a mouse monoclonal antibody and the DAKO alkaline phosphatase–antialkaline phosphatase method. B, Photomicrograph (×640) demonstrating immunoreactive SCF protein in cultured NpFbs. Some fibroblasts showed stronger staining intensity than others (arrow). C, Photomicrograph (×640) demonstrating lack of staining with control protein (mouse IgG 1 myeloma protein). D, Photomicrograph (×640) demonstrating immunoreactive SCF protein in ciliated columnar epithelial cells (arrow) and goblet cells (arrowhead) in a nasal brushing from a subject with AR. E, Photomicrograph (×640) demonstrating decrease of immunoreactive SCF protein in most of ciliated columnar cells and goblet cells in a nasal brushing from a control subject. F, Photomicrograph (×640) demonstrating lack of immunoreactive SCF protein in a nasal brushing preincubated with control antibody (mouse IgG 1 myeloma protein). G, Photomicrograph (×400) demonstrating immunoreactive SCF protein in most NpEps. H, Photomicrograph (×400) demonstrating immunoreactive SCF protein in stromal endothelial cells (arrow), a fibroblast (filled arrowhead), and a mononuclear cell (open arrowhead). I, Photomicrograph (×200) demonstrating no staining with control antibody (mouse IgG 1 myeloma protein). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

7 Fig. 4 Immunohistochemical localization of SCF in nasal tissues. A, Photomicrograph (×640) demonstrating immunoreactive SCF protein diffusely in cytoplasm of cultured NpEps with a mouse monoclonal antibody and the DAKO alkaline phosphatase–antialkaline phosphatase method. B, Photomicrograph (×640) demonstrating immunoreactive SCF protein in cultured NpFbs. Some fibroblasts showed stronger staining intensity than others (arrow). C, Photomicrograph (×640) demonstrating lack of staining with control protein (mouse IgG 1 myeloma protein). D, Photomicrograph (×640) demonstrating immunoreactive SCF protein in ciliated columnar epithelial cells (arrow) and goblet cells (arrowhead) in a nasal brushing from a subject with AR. E, Photomicrograph (×640) demonstrating decrease of immunoreactive SCF protein in most of ciliated columnar cells and goblet cells in a nasal brushing from a control subject. F, Photomicrograph (×640) demonstrating lack of immunoreactive SCF protein in a nasal brushing preincubated with control antibody (mouse IgG 1 myeloma protein). G, Photomicrograph (×400) demonstrating immunoreactive SCF protein in most NpEps. H, Photomicrograph (×400) demonstrating immunoreactive SCF protein in stromal endothelial cells (arrow), a fibroblast (filled arrowhead), and a mononuclear cell (open arrowhead). I, Photomicrograph (×200) demonstrating no staining with control antibody (mouse IgG 1 myeloma protein). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

8 Fig. 4 Immunohistochemical localization of SCF in nasal tissues. A, Photomicrograph (×640) demonstrating immunoreactive SCF protein diffusely in cytoplasm of cultured NpEps with a mouse monoclonal antibody and the DAKO alkaline phosphatase–antialkaline phosphatase method. B, Photomicrograph (×640) demonstrating immunoreactive SCF protein in cultured NpFbs. Some fibroblasts showed stronger staining intensity than others (arrow). C, Photomicrograph (×640) demonstrating lack of staining with control protein (mouse IgG 1 myeloma protein). D, Photomicrograph (×640) demonstrating immunoreactive SCF protein in ciliated columnar epithelial cells (arrow) and goblet cells (arrowhead) in a nasal brushing from a subject with AR. E, Photomicrograph (×640) demonstrating decrease of immunoreactive SCF protein in most of ciliated columnar cells and goblet cells in a nasal brushing from a control subject. F, Photomicrograph (×640) demonstrating lack of immunoreactive SCF protein in a nasal brushing preincubated with control antibody (mouse IgG 1 myeloma protein). G, Photomicrograph (×400) demonstrating immunoreactive SCF protein in most NpEps. H, Photomicrograph (×400) demonstrating immunoreactive SCF protein in stromal endothelial cells (arrow), a fibroblast (filled arrowhead), and a mononuclear cell (open arrowhead). I, Photomicrograph (×200) demonstrating no staining with control antibody (mouse IgG 1 myeloma protein). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

9 Fig. 4 Immunohistochemical localization of SCF in nasal tissues. A, Photomicrograph (×640) demonstrating immunoreactive SCF protein diffusely in cytoplasm of cultured NpEps with a mouse monoclonal antibody and the DAKO alkaline phosphatase–antialkaline phosphatase method. B, Photomicrograph (×640) demonstrating immunoreactive SCF protein in cultured NpFbs. Some fibroblasts showed stronger staining intensity than others (arrow). C, Photomicrograph (×640) demonstrating lack of staining with control protein (mouse IgG 1 myeloma protein). D, Photomicrograph (×640) demonstrating immunoreactive SCF protein in ciliated columnar epithelial cells (arrow) and goblet cells (arrowhead) in a nasal brushing from a subject with AR. E, Photomicrograph (×640) demonstrating decrease of immunoreactive SCF protein in most of ciliated columnar cells and goblet cells in a nasal brushing from a control subject. F, Photomicrograph (×640) demonstrating lack of immunoreactive SCF protein in a nasal brushing preincubated with control antibody (mouse IgG 1 myeloma protein). G, Photomicrograph (×400) demonstrating immunoreactive SCF protein in most NpEps. H, Photomicrograph (×400) demonstrating immunoreactive SCF protein in stromal endothelial cells (arrow), a fibroblast (filled arrowhead), and a mononuclear cell (open arrowhead). I, Photomicrograph (×200) demonstrating no staining with control antibody (mouse IgG 1 myeloma protein). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

10 Fig. 4 Immunohistochemical localization of SCF in nasal tissues. A, Photomicrograph (×640) demonstrating immunoreactive SCF protein diffusely in cytoplasm of cultured NpEps with a mouse monoclonal antibody and the DAKO alkaline phosphatase–antialkaline phosphatase method. B, Photomicrograph (×640) demonstrating immunoreactive SCF protein in cultured NpFbs. Some fibroblasts showed stronger staining intensity than others (arrow). C, Photomicrograph (×640) demonstrating lack of staining with control protein (mouse IgG 1 myeloma protein). D, Photomicrograph (×640) demonstrating immunoreactive SCF protein in ciliated columnar epithelial cells (arrow) and goblet cells (arrowhead) in a nasal brushing from a subject with AR. E, Photomicrograph (×640) demonstrating decrease of immunoreactive SCF protein in most of ciliated columnar cells and goblet cells in a nasal brushing from a control subject. F, Photomicrograph (×640) demonstrating lack of immunoreactive SCF protein in a nasal brushing preincubated with control antibody (mouse IgG 1 myeloma protein). G, Photomicrograph (×400) demonstrating immunoreactive SCF protein in most NpEps. H, Photomicrograph (×400) demonstrating immunoreactive SCF protein in stromal endothelial cells (arrow), a fibroblast (filled arrowhead), and a mononuclear cell (open arrowhead). I, Photomicrograph (×200) demonstrating no staining with control antibody (mouse IgG 1 myeloma protein). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

11 Fig. 4 Immunohistochemical localization of SCF in nasal tissues. A, Photomicrograph (×640) demonstrating immunoreactive SCF protein diffusely in cytoplasm of cultured NpEps with a mouse monoclonal antibody and the DAKO alkaline phosphatase–antialkaline phosphatase method. B, Photomicrograph (×640) demonstrating immunoreactive SCF protein in cultured NpFbs. Some fibroblasts showed stronger staining intensity than others (arrow). C, Photomicrograph (×640) demonstrating lack of staining with control protein (mouse IgG 1 myeloma protein). D, Photomicrograph (×640) demonstrating immunoreactive SCF protein in ciliated columnar epithelial cells (arrow) and goblet cells (arrowhead) in a nasal brushing from a subject with AR. E, Photomicrograph (×640) demonstrating decrease of immunoreactive SCF protein in most of ciliated columnar cells and goblet cells in a nasal brushing from a control subject. F, Photomicrograph (×640) demonstrating lack of immunoreactive SCF protein in a nasal brushing preincubated with control antibody (mouse IgG 1 myeloma protein). G, Photomicrograph (×400) demonstrating immunoreactive SCF protein in most NpEps. H, Photomicrograph (×400) demonstrating immunoreactive SCF protein in stromal endothelial cells (arrow), a fibroblast (filled arrowhead), and a mononuclear cell (open arrowhead). I, Photomicrograph (×200) demonstrating no staining with control antibody (mouse IgG 1 myeloma protein). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

12 Fig. 4 Immunohistochemical localization of SCF in nasal tissues. A, Photomicrograph (×640) demonstrating immunoreactive SCF protein diffusely in cytoplasm of cultured NpEps with a mouse monoclonal antibody and the DAKO alkaline phosphatase–antialkaline phosphatase method. B, Photomicrograph (×640) demonstrating immunoreactive SCF protein in cultured NpFbs. Some fibroblasts showed stronger staining intensity than others (arrow). C, Photomicrograph (×640) demonstrating lack of staining with control protein (mouse IgG 1 myeloma protein). D, Photomicrograph (×640) demonstrating immunoreactive SCF protein in ciliated columnar epithelial cells (arrow) and goblet cells (arrowhead) in a nasal brushing from a subject with AR. E, Photomicrograph (×640) demonstrating decrease of immunoreactive SCF protein in most of ciliated columnar cells and goblet cells in a nasal brushing from a control subject. F, Photomicrograph (×640) demonstrating lack of immunoreactive SCF protein in a nasal brushing preincubated with control antibody (mouse IgG 1 myeloma protein). G, Photomicrograph (×400) demonstrating immunoreactive SCF protein in most NpEps. H, Photomicrograph (×400) demonstrating immunoreactive SCF protein in stromal endothelial cells (arrow), a fibroblast (filled arrowhead), and a mononuclear cell (open arrowhead). I, Photomicrograph (×200) demonstrating no staining with control antibody (mouse IgG 1 myeloma protein). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

13 Fig. 4 Immunohistochemical localization of SCF in nasal tissues. A, Photomicrograph (×640) demonstrating immunoreactive SCF protein diffusely in cytoplasm of cultured NpEps with a mouse monoclonal antibody and the DAKO alkaline phosphatase–antialkaline phosphatase method. B, Photomicrograph (×640) demonstrating immunoreactive SCF protein in cultured NpFbs. Some fibroblasts showed stronger staining intensity than others (arrow). C, Photomicrograph (×640) demonstrating lack of staining with control protein (mouse IgG 1 myeloma protein). D, Photomicrograph (×640) demonstrating immunoreactive SCF protein in ciliated columnar epithelial cells (arrow) and goblet cells (arrowhead) in a nasal brushing from a subject with AR. E, Photomicrograph (×640) demonstrating decrease of immunoreactive SCF protein in most of ciliated columnar cells and goblet cells in a nasal brushing from a control subject. F, Photomicrograph (×640) demonstrating lack of immunoreactive SCF protein in a nasal brushing preincubated with control antibody (mouse IgG 1 myeloma protein). G, Photomicrograph (×400) demonstrating immunoreactive SCF protein in most NpEps. H, Photomicrograph (×400) demonstrating immunoreactive SCF protein in stromal endothelial cells (arrow), a fibroblast (filled arrowhead), and a mononuclear cell (open arrowhead). I, Photomicrograph (×200) demonstrating no staining with control antibody (mouse IgG 1 myeloma protein). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

14 Fig. 4 Immunohistochemical localization of SCF in nasal tissues. A, Photomicrograph (×640) demonstrating immunoreactive SCF protein diffusely in cytoplasm of cultured NpEps with a mouse monoclonal antibody and the DAKO alkaline phosphatase–antialkaline phosphatase method. B, Photomicrograph (×640) demonstrating immunoreactive SCF protein in cultured NpFbs. Some fibroblasts showed stronger staining intensity than others (arrow). C, Photomicrograph (×640) demonstrating lack of staining with control protein (mouse IgG 1 myeloma protein). D, Photomicrograph (×640) demonstrating immunoreactive SCF protein in ciliated columnar epithelial cells (arrow) and goblet cells (arrowhead) in a nasal brushing from a subject with AR. E, Photomicrograph (×640) demonstrating decrease of immunoreactive SCF protein in most of ciliated columnar cells and goblet cells in a nasal brushing from a control subject. F, Photomicrograph (×640) demonstrating lack of immunoreactive SCF protein in a nasal brushing preincubated with control antibody (mouse IgG 1 myeloma protein). G, Photomicrograph (×400) demonstrating immunoreactive SCF protein in most NpEps. H, Photomicrograph (×400) demonstrating immunoreactive SCF protein in stromal endothelial cells (arrow), a fibroblast (filled arrowhead), and a mononuclear cell (open arrowhead). I, Photomicrograph (×200) demonstrating no staining with control antibody (mouse IgG 1 myeloma protein). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

15 Fig. 5 Regression analysis of relationship between numbers of immunoreactive SCF protein-positive cells and intensity indices of SCF staining in Nps. The relationship is statistically significant (r = 0.81, p = ). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

16 Fig. 6 Effect of budesonide on SCF production by unstimulated and IL-1-stimulated primary fibroblast cell lines. Budesonide inhibited, in a dose-response fashion, SCF production only by unstimulated primary fibroblast cell lines (nos. 1 and 2) but had no inhibitory effect on either IL-1-stimulated (cell line no. 2) or transformed HeLa or NCi-H69 cells (results of two experiments, mean of replicate samples for each experiment, p < .05). Journal of Allergy and Clinical Immunology  , DOI: ( /S (97) ) Copyright © 1997 Mosby, Inc. Terms and Conditions

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