Cell and Tissue Research

, Volume 318, Issue 3, pp 579–589

Extracellular matrix distribution and islet morphology in the early postnatal pancreas: anomalies in the non-obese diabetic mouse

  • Sacha Brigitte Geutskens
  • Françoise Homo-Delarche
  • Jean-Marie Pleau
  • Sylvie Durant
  • Hemmo Arjan Drexhage
  • Wilson Savino
Regular Article

DOI: 10.1007/s00441-004-0989-0

Cite this article as:
Geutskens, S.B., Homo-Delarche, F., Pleau, J. et al. Cell Tissue Res (2004) 318: 579. doi:10.1007/s00441-004-0989-0

Abstract

Previously, we reported elevated numbers of macrophages in the pancreas of NOD mice, a spontaneous animal model for T1D, during the early postnatal period. Extracellular matrix plays an important role in the tissue trafficking and retention of macrophages as well as in postnatal pancreas development. Therefore, we have examined the expression and distribution of laminin and fibronectin, two major extracellular matrix proteins and their corresponding integrin receptors, in the pre-weaning pancreases of NOD mice and control mouse strains. In addition, we have characterized the pancreas morphology during this period, since the morphology of the pre-weaning pancreas before the onset of lymphocytic peri-insulitis, when the pancreas is still subject to developmental changes, has been poorly documented. We show that laminin labeling is mainly associated with exocrine tissue, whereas fibronectin labeling was mostly localized at the islet-ductal pole, islet periphery and in intralobular septa. Moreover, the protein expression level of fibronectin was increased in NOD pancreases at the early stage of postnatal development, as compared to pancreases of C57BL/6 and BALB/c mouse strains. Interestingly, pancreatic macrophages were essentially found at sites of intense fibronectin labeling. The increased fibronectin content in NOD neonatal pancreas coincided with altered islet morphology, histologically reflected by enlarged and irregular shaped islets and increased percentages of total endocrine area as compared to that of control strains. In conclusion, increased levels of the extracellular matrix protein fibronectin were found in the early postnatal NOD pancreas, and this is associated with an enhanced accumulation of macrophages and altered islet morphology.

Keywords

Pre-weaning pancreasExtracellular matrixMacrophagesIslet morphologyMouse (NOD; C57BL/6; BALB/C)

Abbreviations:

BMDMs

Bone marrow-derived macrophages

ECM

Extracellular matrix

HE

Hematoxylin-eosin

M-CSF

Macrophage-colony stimulating factor

NOD

Non-obese diabetic

T1D

Type 1 diabetes

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Sacha Brigitte Geutskens
    • 1
    • 2
  • Françoise Homo-Delarche
    • 3
  • Jean-Marie Pleau
    • 2
  • Sylvie Durant
    • 4
  • Hemmo Arjan Drexhage
    • 1
  • Wilson Savino
    • 2
    • 5
  1. 1.Department of ImmunologyErasmus MCRotterdamThe Netherlands
  2. 2.CNRS UMR 8147, Necker HospitalParis V UniversityParisFrance
  3. 3.CNRS UMR 7059Paris VII University/D.DiderotParisFrance
  4. 4.INSERM U530Centre Universitaire-UFR biomédicaleParisFrance
  5. 5.Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz InstituteOswaldo Cruz FoundationRio de JaneiroBrazil