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Interaction of Transforming Growth Factor ß (TGFß) with Proteinase 3

  • J. Kekow
  • E. Csernok
  • C. Szymkowiak
  • W. L. Gross
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 421)

Summary

TGFß is a multifunctional cytokine modulating onset and course of autoimmune diseases as shown in experimental models. Aim of this study was to investigate possible interactions of TGFß with lysosomal enzymes identified as ANCA autoantigens (e.g. proteinase 3, PR3). This included TGFß effects on the translocation the lysosomal enzymes to the cell surface ofpolymorphonuclear cells (PMN), and the presumabe activation of non bioactive, latent TGFß by these enzymes. Flow cytometry analysis showed TGFß1 to be a potent translocation factor for PR3 comparable with other neutrophil activating factors such as irtterleukin 8 (1 L8). The PR3 membrane expression on primed PMN increased by up to 51% after incubation with TGFß1. PR3 itself was revealed as a potent activator of latent TGFß, thus mediating bioeffects of this cytokine. Patients with various types of systemic vasculitis (SV) showed marked TGFß overexpression correlating with disease. Mean TGFßI plasma levels in the ANCA associated vasculitis (AAV) patients ranged from 8.9 (Wegeners granulomatosis, WG) to 13.3 ng/ml (Churg-Strauss syndrome, CSS) (control: 4.2 ng/ml, p<0.01) while TGFß2 levels were not elevated. Our findings, together with other features of TGFß’s such as induction of angiogenesis and its strong chemotactic capacity, indicate that TGFß might serve as a proinflammatory factor in SV, especially in AAV.

Keywords

Rheumatoid Arthritis Lysosomal Enzyme Systemic Vasculitis ANCA Associate Vasculitis Vasculitis Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • J. Kekow
    • 1
  • E. Csernok
    • 2
  • C. Szymkowiak
    • 2
  • W. L. Gross
    • 2
  1. 1.Clinic of RheumatologyOtto von Guericke University of MagdeburgVogelsangGermany
  2. 2.Department of Clinical Rheumatology and Rheumaklinik Bad Bramstedt GmbHMedical University of LübeckLübeckGermany

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