PMID- 17130538
OWN - NLM
STAT- MEDLINE
DCOM- 20070110
LR  - 20131121
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1079
DP  - 2006 Oct
TI  - Immunolocalization of monocyte chemoattractant protein-1 in islets of NOD mice 
      during cyclophosphamide administration.
PG  - 103-8
AB  - The molecular processes that initiate insulitis in type 1 diabetes remain 
      unclear. Chemokines, such as monocyte chemoattractant protein-1 (MCP-1), mediate 
      chemotaxis and leukocyte migration to inflammatory sites. Although MCP-1 mRNA has 
      been shown in islets isolated from NOD mice at 2 weeks of age and at later 
      stages, the cellular sources of this chemokine, at the protein level, and its 
      role in insulitis are unclear. The aims of the present study were to employ 
      immunohistochemical techniques to examine the expression of MCP-1 and quantify 
      its cellular sources in islets of NOD mice both after cyclophosphamide (Cy) 
      administration and in spontaneous diabetes. Tissues were examined at days 1 (=day 
      73, first day of Cy), 4, 7, 11, and 14 and in age-matched control NOD mice. 
      Pancreatic sections from NOD mice without Cy administration were also studied 
      between days 21-65 and at onset of diabetes and from adult CD-1 mice. In the Cy 
      group, a small number of peri-islet macrophages were immunopositive for MCP-1 at 
      day 1 whereas at day 4, the number declined but increased subsequently at day 7. 
      In the same group, it increased markedly at days 11 and 14 compared with 
      age-matched control NOD mice. In young NOD mice, MCP-1 was present in selective 
      macrophages in islets with early insulitis (day 45) but was absent at diabetes 
      onset. MCP-1 was undetectable in beta cells and in most T cells. Islets from 
      adult CD-1 mice did not show immunostaining for MCP-1. We conclude that MCP-1 is 
      expressed in a proportion of islet and exocrine macrophages. This expression 
      increases during the later stages of Cy-induced diabetes. Thus, MCP-1 positive 
      macrophages that migrate to the islet periphery during the early stages of 
      Cy-induced diabetes and preceding spontaneous diabetes may augment insulitis by 
      further attracting macrophages and T cells.
FAU - Reddy, Shiva
AU  - Reddy S
AD  - School of Biological Sciences, University of Auckland, Auckland, New Zealand. 
      s.reddy@auckland.ac.nz
FAU - Bai, Yan
AU  - Bai Y
FAU - Robinson, Elizabeth
AU  - Robinson E
FAU - Ross, Jacqueline
AU  - Ross J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Chemokine CCL2)
RN  - 0 (Immunosuppressive Agents)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*metabolism
MH  - Cyclophosphamide/administration & dosage/*toxicity
MH  - Diabetes Mellitus, Experimental/chemically induced/genetics/metabolism
MH  - Female
MH  - *Immunohistochemistry
MH  - Immunosuppressive Agents/administration & dosage/*toxicity
MH  - Islets of Langerhans/*drug effects/metabolism/pathology
MH  - Macrophages/drug effects/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Time Factors
EDAT- 2006/11/30 09:00
MHDA- 2007/01/11 09:00
CRDT- 2006/11/30 09:00
PHST- 2006/11/30 09:00 [pubmed]
PHST- 2007/01/11 09:00 [medline]
PHST- 2006/11/30 09:00 [entrez]
AID - 1079/1/103 [pii]
AID - 10.1196/annals.1375.014 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2006 Oct;1079:103-8. doi: 10.1196/annals.1375.014.