PMID- 17214704
OWN - NLM
STAT- MEDLINE
DCOM- 20070302
LR  - 20220224
IS  - 0908-665X (Print)
IS  - 0908-665X (Linking)
VI  - 14
IP  - 1
DP  - 2007 Jan
TI  - Chemokine and toll-like receptor signaling in macrophage mediated islet xenograft 
      rejection.
PG  - 48-59
AB  - BACKGROUND: Adoptive transfer of antigen-primed T-cell-activated macrophages into 
      NOD-SCID mice within 14 days of foetal porcine pancreatic fragment (FPP) or 
      foetal porcine skin (FPS) transplantation had been shown to cause xenograft 
      rejection. In the present study, it was proposed that signaling between the graft 
      and macrophages promoted specific graft recognition and destruction in this 
      setting. METHODS: Exogenous macrophages isolated from rejecting FPP xenografts 
      were transferred to NOD-SCID FPP recipients and tracked by Ly5.1 surface antigen 
      or via CSFE staining. Monocyte chemoattractant protein-1 (MCP-1), macrophage 
      inflammatory protein-1alpha (MIP-1alpha), macrophage inflammatory protein-1beta 
      (MIP-1beta), regulated upon activation, normal T-cell expressed and secreted 
      (RANTES), chemokine (C-C motif) receptor 2 (CCR2), chemokine (C-C motif) receptor 
      5 (CCR5), toll-like receptors (TLRs) (1-9) and gene expression in transplanted 
      FPP xenografts was evaluated by real-time polymerase chain reaction. Gene 
      expression of CCR2, CCR5 and TLRs was also analyzed in pooled samples of 
      activated and non-activated macrophages. RESULTS: Exogenous macrophages were 
      shown to track to and reject recently transplanted but not established FPP 
      xenografts. Gene expression for MCP-1, RANTES, MIP-1alpha and MIP-1beta was at 
      least 3-fold greater in recently transplanted compared with established 
      xenografts (P < 0.05), and CCR2 and CCR5 gene expression was 10-fold greater in 
      activated compared non-activated macrophages, suggesting that graft-mediated 
      pro-inflammatory signals were important for macrophage recruitment. Specific 
      graft recognition by macrophages may involve TLR signaling as macrophages exposed 
      to porcine islets had higher levels of TLR gene expression compared with those 
      exposed to allografts regardless of the level of activation. CONCLUSION: 
      Xenografts provide additional activation signals to macrophages that are not seen 
      following allotransplantation. This study identifies chemokines and TLR as 
      important signals in macrophage-mediated recognition and rejection of islet 
      xenografts.
FAU - Chandra, Abhilash P
AU  - Chandra AP
AD  - Centre for Transplant and Renal Research, Westmead Millenium Institute, 
      University of Sydney at Westmead Hospital, Westmead, Australia.
FAU - Ouyang, Li
AU  - Ouyang L
FAU - Yi, Shounan
AU  - Yi S
FAU - Wong, Jeffrey K W
AU  - Wong JK
FAU - Ha, Hong
AU  - Ha H
FAU - Walters, Stacey N
AU  - Walters SN
FAU - Patel, Anita T
AU  - Patel AT
FAU - Stokes, Rebecca
AU  - Stokes R
FAU - Jardine, Meg
AU  - Jardine M
FAU - Hawthorne, Wayne J
AU  - Hawthorne WJ
FAU - O'Connell, Philip J
AU  - O'Connell PJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - Xenotransplantation
JT  - Xenotransplantation
JID - 9438793
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokines)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cell Movement
MH  - Chemokines/immunology/*metabolism
MH  - Female
MH  - Gene Expression
MH  - Graft Rejection/*immunology/metabolism
MH  - Islets of Langerhans Transplantation/adverse effects/*immunology/pathology
MH  - Macrophages/cytology/*immunology/metabolism
MH  - Mice
MH  - Receptors, CCR2
MH  - Receptors, CCR5/genetics/immunology
MH  - Receptors, Chemokine/genetics/immunology
MH  - Signal Transduction/*immunology
MH  - Skin/immunology/metabolism
MH  - Swine
MH  - Toll-Like Receptors/genetics/*metabolism
MH  - Transplantation, Heterologous/*immunology
MH  - Up-Regulation
EDAT- 2007/01/12 09:00
MHDA- 2007/03/03 09:00
CRDT- 2007/01/12 09:00
PHST- 2007/01/12 09:00 [pubmed]
PHST- 2007/03/03 09:00 [medline]
PHST- 2007/01/12 09:00 [entrez]
AID - XEN363 [pii]
AID - 10.1111/j.1399-3089.2006.00363.x [doi]
PST - ppublish
SO  - Xenotransplantation. 2007 Jan;14(1):48-59. doi: 10.1111/j.1399-3089.2006.00363.x.