Chemokine expression in nerve allografts.
OBJECTIVE
Chemokines (chemoattractant cytokines) play a major role in trafficking of cells to areas of inflammation. Infiltration of allograft tissues by immunocompetent cells is critical for rejection of donor tissues. The role of chemokines in nerve allograft rejection is not clear. We hypothesized that chemokines are responsible for attracting macrophages and T lymphocytes into nerve allograft tissue, initiating the graft rejection process.


METHODS
Lewis rats received 4-cm-long peroneal nerve allografts and isografts from ACI and Lewis rats, respectively. Twelve hours to 10 days after transplantation, grafts were removed and total cellular ribonucleic acid was extracted. Intragraft gene expression of several chemokines (cytokine-induced neutrophil chemoattractant, macrophage inflammatory protein [MIP]-2, monocyte chemoattractant protein-1, MIP-1 alpha, and regulated upon activation normal T-cell expressed and secreted [RANTES]) were analyzed by reverse transcription-polymerase chain reaction.


RESULTS
The cytokine-induced neutrophil chemoattractant was expressed in allografts and isografts at early time points (12 h to 6 d). Monocyte chemoattractant protein-1 messenger ribonucleic acid expression was similarly high in both isografts and allografts from 12 hours until 8 days after transplantation. MIP-1 alpha, MIP-2, and RANTES were expressed only in allografts. Kinetics of the neutrophil (MIP-2) and macrophage (MIP-1 alpha) chemokines revealed an early onset (12-24 h), a plateau from 1 to 4 days, and expression abruptly declining by Day 6. The lymphocyte chemoattractant RANTES had delayed kinetics, with a rise at Day 3, a peak at Day 4, and a gradual decline.


CONCLUSIONS
Induction of specific chemokine genes precedes nerve allograft infiltration by immunocompetent cells. MIP-1 alpha, MIP-2, and RANTES may be responsible for recruiting macrophages, granulocytes, and lymphocytes, respectively, to the rejecting allograft. In future studies, blockade of these specific chemokines or their receptors may prove to delay or prevent nerve allograft rejection.
Midha
Rajiv
R
Division of Neurosurgery and Neuroscience Research Program, Department of Surgery, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. rajiv.madha@sw.ca
Munro
Catherine A
CA
Ramakrishna
Vankayalapati
V
Matsuyama
Takeshi
T
Gorczynski
Reginald M
RM
D000818:Animals; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D010543:Peroneal Nerve / Q000378:metabolism* / Q000637:transplantation*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D019742:Chemokines, CC; D019743:Chemokines, CXC; D012333:RNA, Messenger