TY - JOUR
T1 - The role of recipient mast cells in acute and chronic cardiac allograft rejection in C57BL/6-KitW-sh/W-sh mice
AU - Itoh, Satoshi
AU - Nakae, Susumu
AU - Velotta, Jeffrey B.
AU - Kosuge, Hisanori
AU - Connolly, Andrew
AU - Tsai, Mindy
AU - Adachi, Hideo
AU - Galli, Stephen J.
AU - Robbins, Robert C.
AU - Fischbein, Michael P.
N1 - Funding Information:
This study was supported by the Falk Research Fund for the Department of Cardiothoracic Surgery at Stanford University Medical School , an ISHLT Research Fellowship Award to Dr Itoh, and United States Public Health Service grants AI23990 , AI070813 , and CA72074 to Dr Galli.
PY - 2010/4
Y1 - 2010/4
N2 - Background: Mast cells are hypothesized to promote rejection and adverse remodeling in cardiac allografts. In contrast, it has been reported that mast cells may enhance cardiac allograft survival in rats. We used C57BL/6-KitW-sh/W-sh mast cell-deficient and corresponding wild-type mice to investigate possible contributions of recipient mast cells to acute or chronic cardiac allograft rejection. Methods: FVB (H-2q; acute rejection), or C-H-2bm12KhEg (H-2bm12; chronic rejection) donor hearts were heterotopically transplanted into C57BL/6-KitW-sh/W-sh (H-2b) or C57BL/6-Kit+/+ (H-2b) mice. The degree of acute rejection was assessed at 5 days and chronic rejection, at 52 days. Results: In the acute rejection model, donor heart vascular cell adhesion molecule-1 (VCAM-1) expression was significantly lower in C57BL/6-KitW-sh/W-sh than in wild-type recipients; however, acute rejection scores, graft survival, inflammatory cells, or cytokine expression did not differ significantly. In the chronic rejection model, the number of mast cells/mm2 of allograft tissue was significantly increased 52 days after transplantation in allografts transplanted into C57BL/6-Kit+/+ but not C57BL/6-KitW-sh/W-sh mice; however, no substantial differences were noted in graft coronary artery disease, graft inflammatory cells, or levels of graft tissue expression of cytokines or adhesion molecules. Conclusions: Cardiac allografts undergoing chronic rejection in wild-type C57BL/6-Kit+/+ mice exhibit increased numbers of mast cells, but acute or chronic cardiac allograft rejection can develop in C57BL/6-KitW-sh/W-sh mice even though these recipients virtually lack mast cells. These findings indicate that recipient mast cells are not required for acute or chronic cardiac allograft rejection in the models examined.
AB - Background: Mast cells are hypothesized to promote rejection and adverse remodeling in cardiac allografts. In contrast, it has been reported that mast cells may enhance cardiac allograft survival in rats. We used C57BL/6-KitW-sh/W-sh mast cell-deficient and corresponding wild-type mice to investigate possible contributions of recipient mast cells to acute or chronic cardiac allograft rejection. Methods: FVB (H-2q; acute rejection), or C-H-2bm12KhEg (H-2bm12; chronic rejection) donor hearts were heterotopically transplanted into C57BL/6-KitW-sh/W-sh (H-2b) or C57BL/6-Kit+/+ (H-2b) mice. The degree of acute rejection was assessed at 5 days and chronic rejection, at 52 days. Results: In the acute rejection model, donor heart vascular cell adhesion molecule-1 (VCAM-1) expression was significantly lower in C57BL/6-KitW-sh/W-sh than in wild-type recipients; however, acute rejection scores, graft survival, inflammatory cells, or cytokine expression did not differ significantly. In the chronic rejection model, the number of mast cells/mm2 of allograft tissue was significantly increased 52 days after transplantation in allografts transplanted into C57BL/6-Kit+/+ but not C57BL/6-KitW-sh/W-sh mice; however, no substantial differences were noted in graft coronary artery disease, graft inflammatory cells, or levels of graft tissue expression of cytokines or adhesion molecules. Conclusions: Cardiac allografts undergoing chronic rejection in wild-type C57BL/6-Kit+/+ mice exhibit increased numbers of mast cells, but acute or chronic cardiac allograft rejection can develop in C57BL/6-KitW-sh/W-sh mice even though these recipients virtually lack mast cells. These findings indicate that recipient mast cells are not required for acute or chronic cardiac allograft rejection in the models examined.
KW - acute rejection
KW - chronic rejection
KW - mast cells
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U2 - 10.1016/j.healun.2009.08.019
DO - 10.1016/j.healun.2009.08.019
M3 - Article
C2 - 19818646
AN - SCOPUS:77949567228
SN - 1053-2498
VL - 29
SP - 401
EP - 409
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 4
ER -