TY - JOUR
T1 - Rat cytomegalovirus-accelerated transplant vascular sclerosis is reduced with mutation of the chemokine-receptor R33
AU - Streblow, Daniel N.
AU - Kreklywich, Craig N.
AU - Smith, Patricia
AU - Soule, Jordana L.
AU - Meyer, Christine
AU - Yin, Qiang (Michael)
AU - Beisser, Patrick
AU - Vink, Cornelis
AU - Nelson, Jay
AU - Orloff, Susan L.
PY - 2005/3
Y1 - 2005/3
N2 - Cytomegalovirus (CMV) infection accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in both human and animal solid organ transplantation models. The host/viral mechanisms involved in this process are unclear. We examine the role of the rat CMV (RCMV)-encoded chemokine-receptor R33 in the development of TVS using a rat heart transplantation/CR model. F344 heart grafts were transplanted heterotopically into Lewis recipients. The ability of RCMV lacking the R33 gene (RCMV-Δr33) to accelerate CR/TVS (neointimal index, NI) was compared to wild-type (WT) RCMV. Allograft recipients were infected with 1 × 105 pfu RCMV or RCMV-Δr33 on postoperative day (POD) 1. Grafts from RCWV-Δr33-infected recipients demonstrated an accelerated time to allograft CR compared to grafts from uninfected recipients (POD = 56 vs. 90), this was slower than that seen in grafts from WT-RCMV-infected recipients (POD = 45). Similarly, the degree of graft TVS formation at terminal rejection in RMCV-Δr33 infected recipients was more severe than uninfected recipients (NI = 63 vs. 45), yet not as severe as in WT-RCMV infected recipients (NI = 83). In parallel, RCMV-Δr33 failed to induce vascular smooth muscle cell (SMC) migration in vitro, whereas WT-RCMV induced substantial migration. The RCMV-encoded chemokine-recepfor r33 is critical for RCMV-accelerated TVS/CR and vascular SMC migration.
AB - Cytomegalovirus (CMV) infection accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in both human and animal solid organ transplantation models. The host/viral mechanisms involved in this process are unclear. We examine the role of the rat CMV (RCMV)-encoded chemokine-receptor R33 in the development of TVS using a rat heart transplantation/CR model. F344 heart grafts were transplanted heterotopically into Lewis recipients. The ability of RCMV lacking the R33 gene (RCMV-Δr33) to accelerate CR/TVS (neointimal index, NI) was compared to wild-type (WT) RCMV. Allograft recipients were infected with 1 × 105 pfu RCMV or RCMV-Δr33 on postoperative day (POD) 1. Grafts from RCWV-Δr33-infected recipients demonstrated an accelerated time to allograft CR compared to grafts from uninfected recipients (POD = 56 vs. 90), this was slower than that seen in grafts from WT-RCMV-infected recipients (POD = 45). Similarly, the degree of graft TVS formation at terminal rejection in RMCV-Δr33 infected recipients was more severe than uninfected recipients (NI = 63 vs. 45), yet not as severe as in WT-RCMV infected recipients (NI = 83). In parallel, RCMV-Δr33 failed to induce vascular smooth muscle cell (SMC) migration in vitro, whereas WT-RCMV induced substantial migration. The RCMV-encoded chemokine-recepfor r33 is critical for RCMV-accelerated TVS/CR and vascular SMC migration.
KW - Chemokine receptor
KW - Cytomegalovirus
KW - Transplant vascular sclerosis (TVS)
KW - Transplant vasculopathy
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U2 - 10.1111/j.1600-6143.2004.00711.x
DO - 10.1111/j.1600-6143.2004.00711.x
M3 - Article
C2 - 15707397
AN - SCOPUS:20044394710
SN - 1600-6135
VL - 5
SP - 436
EP - 442
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 3
ER -