PMID- 14962280
OWN - NLM
STAT- MEDLINE
DCOM- 20041122
LR  - 20061115
IS  - 0908-665X (Print)
IS  - 0908-665X (Linking)
VI  - 11
IP  - 2
DP  - 2004 Mar
TI  - Adult porcine islets produce MCP-1 and recruit human monocytes in vitro.
PG  - 184-94
AB  - Type 1 diabetes can be cured by transplantation of isolated pancreatic islets. 
      Because of the shortage of human donor tissue, adult porcine islets (APIs) 
      constitute a possible alternative tissue source. Upon intraportal injection, 
      islets are subjected to an instant blood-mediated inflammatory reaction (IBMIR) 
      leading to blood clotting, leukocyte islet-infiltration, islet damage and insulin 
      release. Xenogeneic islets surviving IBMIR are rejected in a cellular process 
      involving CD4(+) T lymphocytes and macrophages. We have investigated whether APIs 
      themselves produce and secrete chemokines and/or inflammatory cytokines that may 
      contribute to IBMIR and/or cell-mediated rejection. APIs, cultured for 1, 4, 8 
      and 11 days post-isolation, expressed mRNA for monocyte chemoattractant protein-1 
      (MCP-1), IL-1beta and TNF-alpha. API culture supernatants induced migration of 
      human monocytes, which was significantly blocked by an anti-human MCP-1 antibody 
      (Ab). Immunohistochemistry revealed MCP-1 in the cytoplasm of alpha- and 
      beta-cells in isolated islets and in islets in situ. However, APIs or their 
      supernatants were not able to activate human aortic endothelial cells (HAECs) in 
      vitro, and neither IL-1beta nor TNF-alpha were detected by enzyme-linked 
      immunosorbent assay (ELISA) in API culture supernatants. Both recombinant porcine 
      IL-1beta and TNF-alpha were able to activate human endothelial cells (ECs) 
      inducing CD62E and CD106 expression as analyzed by flow cytometry. In conclusion, 
      MCP-1 secreted by APIs may contribute to both IBMIR and rejection by attracting 
      monocytes into the islet; monocytes which upon transformation into macrophages 
      will potentiate antigen presentation and execute islet rejection.
FAU - Ehrnfelt, Cecilia
AU  - Ehrnfelt C
AD  - Division of Clinical Immunology, Karolinska Institutet, Huddinge University 
      Hospital AB, Stockholm, Sweden. cecilia.ehrnfelt@labmed.ki.se
FAU - Kumagai-Braesch, Makiko
AU  - Kumagai-Braesch M
FAU - Uzunel, Mehmet
AU  - Uzunel M
FAU - Holgersson, Jan
AU  - Holgersson J
LA  - eng
PT  - Journal Article
PL  - Denmark
TA  - Xenotransplantation
JT  - Xenotransplantation
JID - 9438793
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA Primers)
RN  - 0 (Interleukin-1)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Chemokine CCL2/analysis/*biosynthesis/genetics
MH  - Coculture Techniques
MH  - DNA Primers
MH  - Endothelium, Vascular/cytology
MH  - Humans
MH  - Immunohistochemistry
MH  - Interleukin-1/genetics
MH  - Islets of Langerhans/cytology/immunology
MH  - Kinetics
MH  - *Leukocyte Transfusion
MH  - Monocytes/cytology/*immunology
MH  - Pancreas/cytology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Swine
MH  - Transplantation, Heterologous/*immunology
EDAT- 2004/02/14 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/02/14 05:00
PHST- 2004/02/14 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/02/14 05:00 [entrez]
AID - XEN104 [pii]
AID - 10.1046/j.1399-3089.2003.00104.x [doi]
PST - ppublish
SO  - Xenotransplantation. 2004 Mar;11(2):184-94. doi: 
      10.1046/j.1399-3089.2003.00104.x.