The Journal of Heart and Lung Transplantation
Volume 29, Issue 4 , Pages 401-409 , April 2010

The role of recipient mast cells in acute and chronic cardiac allograft rejection in C57BL/6-KitW-sh/W-sh mice

  • Satoshi Itoh, MD

      Affiliations

    • Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California
  • ,
  • Susumu Nakae, PhD

      Affiliations

    • Frontier Research Initiative, The Institute of Medical Science, The University of Tokyo, Tokyo
  • ,
  • Jeffrey B. Velotta, MD

      Affiliations

    • Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California
  • ,
  • Hisanori Kosuge, MD

      Affiliations

    • Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California
  • ,
  • Andrew Connolly, MD

      Affiliations

    • Department of Pathology and Microbiology, and Immunology, Stanford University School of Medicine, Stanford, California
  • ,
  • Mindy Tsai, DMSc

      Affiliations

    • Department of Pathology and Microbiology, and Immunology, Stanford University School of Medicine, Stanford, California
  • ,
  • Hideo Adachi, MD

      Affiliations

    • Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan
  • ,
  • Stephen J. Galli, MD

      Affiliations

    • Department of Pathology and Microbiology, and Immunology, Stanford University School of Medicine, Stanford, California
  • ,
  • Robert C. Robbins, MD

      Affiliations

    • Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California
  • ,
  • Michael P. Fischbein, MD, PhD

      Affiliations

    • Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California
    • Corresponding Author InformationReprint requests: Michael P. Fischbein, MD, PhD, Department of Cardiothoracic Surgery, Stanford University School of Medicine, 300 Pasteur Dr, CVRB MC 5407, Stanford, CA 94305. Telephone: 650-725-3828. Fax: 650-725-3846

  • Image Result

    (A) Survival of cardiac allografts in wild-type (Kit+/+) mice (filled circles; n = 8) or genetically mast cell-deficient (KitW-sh/W-sh) mice (open circles; n = 8) during acute rejection. (B) Survival

    (A) Survival of cardiac allografts in wild-type (Kit+/+) mice (filled circles; n = 8) or genetically mast cell-deficient (KitW-sh/W-sh) mice (open circles; n = 8) during acute rejection. (B) Survival of cardiac allografts from donor Kit+/+ mice (filled circles; n = 6) or mast cell-deficient KitW-sh/W-sh mice (open circles; n = 6) transplanted into FVB recipient mice during acute rejection. (C) Histology of cardiac allografts transplanted into Kit+/+ or mast cell-deficient KitW-sh/W-sh mice at 5 days after transplantation. The bar = 100 μm; hematoxylin and eosin stain; original magnification × 100. (D) Parenchymal rejection (PR) scores at 5 days after transplantation. Data are the mean and standard error of the mean for 8 mice per group. NS, not significant (p > 0.05).

  • Image Result
    (A) Immunohistochemical staining of CD4+, CD8+, and CD11b+ cells in allografts at 5 days after transplantation during acute rejection. The bar = 100 μm; original magnification ×400. (B) Quantitative a

    (A) Immunohistochemical staining of CD4+, CD8+, and CD11b+ cells in allografts at 5 days after transplantation during acute rejection. The bar = 100 μm; original magnification ×400. (B) Quantitative analysis of CD4+, CD8+, and CD11b+ cells. Data are the mean and standard error of the mean of values derived from an analysis of 20 fields.

  • Image Result
    Expression of adhesion molecules, cytokines, and the chemokine monocyte chemotactic protein-1 (MCP-1) is shown during acute rejection in allografts transplanted into Kit+/+ mice (filled bars; n = 6) o

    Expression of adhesion molecules, cytokines, and the chemokine monocyte chemotactic protein-1 (MCP-1) is shown during acute rejection in allografts transplanted into Kit+/+ mice (filled bars; n = 6) or KitW-sh/W-sh mice (open bars; n = 6). *p < 0.05 vs values for Kit+/+ mice. Data show the mean and standard error of the mean in each group. ICAM, intracellular cell adhesion molecule; IFN-γ, interferon-γ; IL, interleukin; VCAM, vascular cell adhesion molecule.

  • Image Result
    (A) Baseline mast cell numbers in non-transplanted donor hearts. (B) Mast cell numbers/mm2 detected in Bm12 allografts transplanted into Bm12 mice (isograft controls). (C) Bm12 allografts transplanted

    (A) Baseline mast cell numbers in non-transplanted donor hearts. (B) Mast cell numbers/mm2 detected in Bm12 allografts transplanted into Bm12 mice (isograft controls). (C) Bm12 allografts transplanted into C57BL/6-KitW-sh/W-sh mice. (D) Mast cell numbers/mm2 in allografts from C57BL/6-Kit+/+ recipients 52 days after transplantation. The error bar shows the standard error of the mean.

  • Image Result
    (A) The graft beating scores of allografts in Kit+/+ mice (filled squares; n = 8) and KitW-sh/W-sh mice (open circles; n = 8) after cardiac transplantation in the chronic rejection model, consisting o

    (A) The graft beating scores of allografts in Kit+/+ mice (filled squares; n = 8) and KitW-sh/W-sh mice (open circles; n = 8) after cardiac transplantation in the chronic rejection model, consisting of an major histocompatibility complex class II mismatch. (B) Elastic Van Gieson-stained representative sections of cardiac allografts undergoing chronic rejection 52 days after transplantation into Kit+/+ or KitW-sh/W-sh mice. Original magnification ×400. (C) Data from morphometric assessment of luminal occlusion, intima/media (I/M) ratio, and diseased vessels in sections like those shown in Panel A. Data are the mean and standard error of the mean for 8 mice per group.

  • Image Result
    (A) Representative sections of cardiac allografts undergoing chronic rejection 52 days after transplantation into Kit+/+ or KitW-sh/W-sh mice. The bar = 100 μm; hematoxylin and eosin stain; original m

    (A) Representative sections of cardiac allografts undergoing chronic rejection 52 days after transplantation into Kit+/+ or KitW-sh/W-sh mice. The bar = 100 μm; hematoxylin and eosin stain; original magnification ×100. (B) Parenchymal rejection (PR) and fibrotic scores in sections like those shown in Panel A. Data are the mean and standard error of the mean (SEM) from 8 mice per group. (C) Quantitative analysis of CD4+, CD8+, and CD11b+ cells. Data are the mean and SEM of values derived from an analysis of 20 fields with 6 mice per group.

PII: S1053-2498(09)00681-0

doi: 10.1016/j.healun.2009.08.019

The Journal of Heart and Lung Transplantation
Volume 29, Issue 4 , Pages 401-409 , April 2010