The role of recipient mast cells in acute and chronic cardiac allograft rejection in C57BL/6-KitW-sh/W-sh mice.
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-Kit(W-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-2(q); acute rejection), or C-H-2(bm12)KhEg (H-2(bm12); chronic rejection) donor hearts were heterotopically transplanted into C57BL/6-Kit(W-sh/W-sh) (H-2(b)) or C57BL/6-Kit(+/+) (H-2(b)) 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-Kit(W-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/mm(2) of allograft tissue was significantly increased 52 days after transplantation in allografts transplanted into C57BL/6-Kit(+/+) but not C57BL/6-Kit(W-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-Kit(W-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.
Itoh
Satoshi
S
Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California 94305, USA.
Nakae
Susumu
S
Velotta
Jeffrey B
JB
Kosuge
Hisanori
H
Connolly
Andrew
A
Tsai
Mindy
M
Adachi
Hideo
H
Galli
Stephen J
SJ
Robbins
Robert C
RC
Fischbein
Michael P
MP
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006085:Graft Survival / Q000502:physiology; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D023421:Models, Animal; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D016207:Cytokines; D019010:Vascular Cell Adhesion Molecule-1