Association between islet xenograft rejection mediated by activated macrophages and upregulated chemokines.
OBJECTIVE
Our previous study has shown that porcine antigen-primed and CD4+ T cells activated macrophages are capable of the Recognition and rejection of porcine xenografts but not mouse allografts, and therefore suggested the involvement of signaling between the graft and macrophages in this specific graft recognition and destruction.


METHODS
NOD-SCID mice were transplanted with fetal pig pancreatic fragment (FPP) before adoptive transfer with exogenous macrophages isolated from rejecting FPP xenografts of BALB/c recipient mice. The exogenous macrophages were tracked by Ly5.1 surface antigen or via CSFE staining. Gene expression of CCR2 and CCR5 and their chemokines in transplanted FPP xenografts was evaluated by real-time PCR.


RESULTS
After the adoptive transfer, recently transplanted but not established FPP xenografts were rejected by exogenous activated macrophages. In the meantime, greater level of chemokine gene expression was detected in recently-transplanted compared with the established xenografts. Furthermore, expression of both CCR2 and CCR5 genes was enhanced significantly in activated macrophages when compared with non-activated macrophages.


CONCLUSIONS
Upregulated chemokines were associated with macrophage recruitment and destruction of islet xenografts.
Chandra
Abhilash P
AP
Centre for Transplantation and Renal Research, Westmead Millenium Institute, University of Sydney at Westmead Hospital, Westmead 2145, Australia.
Ou-Yang
Li
L
Wong
Jeffrey K W
JK
Ha
Hong
H
Walters
Stacey N
SN
Patel
Anita T
AT
Hawthorne
Wayne J
WJ
Yi
Shou-Nan
SN
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics*; D005260:Female; D016332:Fetal Tissue Transplantation / Q000276:immunology / Q000379:methods; D006084:Graft Rejection / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D019742:Chemokines, CC