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Role of macrophages and cytokines in B-cell death

  • Antje Faust
  • Rainer Kleemann
  • Helga Rothe
  • Hubert Kolb
Part of the Rev.Ser.Advs.Research Diab.Animals (Birkhäuser) book series (RSARDA, volume 6)

Abstract

In recent years data have accumulated suggesting an important contribution of macrophages in the pathogenesis of IDDM, participating as primary inductor cells of autoimmunity, or as effector cells of B-cell destruction. In the spontaneously diabetic NOD mouse, macrophages and dendritic cells are the first cells infiltrating at perivascular and peri-insular regions in early insulitis beginning at the age of 3 wk.1,2 These cells start to invade the inner islet tissue at 30 days of age.3 Comparable features were found earlier in prediabetic insulitis of BB rats, with macrophage infiltration preceding and being essential for later invasion of T-lym-phocytes.4 The relevance of macrophages for the initiation of the disease could be shown by prevention of insulitis and diabetes development after modulation of macrophages in vivo by silica administration in both animal models4–7 or by interference with macrophage adhesion receptors.8 The prevention of islet infiltration in NOD mice by silica treatment was dependent on the young age of the recipient.9 These studies indicate the involvement of macrophages in initial steps of the pathogenesis in animal models. Although silica specifically targets macrophages, this does not lead to their elimination. Rather, redirection of monocyte homing to sites of inflammation, silica deposits, and functional impairment of macrophages are seen.

Key words

BB rats NOD mice immunopathogenesis macrophages inducible NO synthase intervention 

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Copyright information

© Birkhäuser Boston 1996

Authors and Affiliations

  • Antje Faust
    • 1
  • Rainer Kleemann
    • 1
  • Helga Rothe
    • 1
  • Hubert Kolb
    • 1
    • 2
  1. 1.Diabetes Research InstituteHeinrich-Heine-University of DusseldorfDusseldorfGermany
  2. 2.Diabetes Research InstituteDüsseldorfGermany

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