Cytomegalovirus-mediated upregulation of chemokine expression correlates with the acceleration of chronic rejection in rat heart transplants.
Cytomegalovirus (CMV) infections have been shown to dramatically affect solid organ transplant graft survival in both human and animal models. Recently, it was demonstrated that rat CMV (RCMV) infection accelerates the development of transplant vascular sclerosis (TVS) in both rat heart and small bowel graft transplants. However, the mechanisms involved in this process are still unclear. In the present study, we determined the kinetics of RCMV-accelerated TVS in a rat heart transplant model. Acute RCMV infection enhances the development of TVS in rat heart allografts, and this process is initiated between 21 and 24 days posttransplantation. The virus is consistently detected in the heart grafts from day 7 until day 35 posttransplantation but is rarely found at the time of graft rejection (day 45 posttransplantation). Grafts from RCMV-infected recipients had upregulation of chemokine expression compared to uninfected controls, and the timing of this increased expression paralleled that of RCMV-accelerated neointimal formation. In addition, graft vessels from RCMV-infected grafts demonstrate the increased infiltration of T cells and macrophages during periods of highest chemokine expression. These results suggest that CMV-induced acceleration of TVS involves the increased graft vascular infiltration of inflammatory cells through enhanced chemokine expression.
Streblow
Daniel N
DN
Departments of Molecular Microbiology, Oregon Health Sciences University, Portland, Oregon 97201, USA.
Kreklywich
Craig
C
Yin
Qiang
Q
De La Melena
V T
VT
Corless
Christopher L
CL
Smith
Patricia A
PA
Brakebill
Christina
C
Cook
Judith W
JW
Vink
Cornelis
C
Bruggeman
Cathrien A
CA
Nelson
Jay A
JA
Orloff
Susan L
SL
D000818:Animals; D054428:Chemokine CX3CL1; D054357:Chemokine CXCL10; D018925:Chemokines / Q000096:biosynthesis*; D019744:Chemokines, C; D020523:Chemokines, CX3C / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000096:biosynthesis; D002908:Chronic Disease; D003587:Cytomegalovirus / Q000472:pathogenicity*; D006084:Graft Rejection / Q000209:etiology*; D016027:Heart Transplantation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D012795:Sialoglycoproteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D015854:Up-Regulation
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D054357:Chemokine CXCL10; D018925:Chemokines; D019744:Chemokines, C; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; C515540:Cx3cl1 protein, rat; D008222:Lymphokines; D008565:Membrane Proteins; D012795:Sialoglycoproteins; C092390:XCL1 protein, human; C018997:lymphotactin; D007371:Interferon-gamma