Interaction of transforming growth factor beta (TGF beta) with proteinase 3.
TGF beta 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 TGF beta with lysosomal enzymes identified as ANCA autoantigens (e.g. proteinase 3, PR3). This included TGF beta effects on the translocation the lysosomal enzymes to the cell surface of polymorphonuclear cells (PMN), and the presumabe activation of non bioactive, latent TGF beta by these enzymes. Flow cytometry analysis showed TGF beta 1 to be a potent translocation factor for PR3 comparable with other neutrophil activating factors such as interleukin 8 (IL8). The PR3 membrane expression on primed PMN increased by up to 51% after incubation with TGF beta 1. PR3 itself was revealed as a potent activator of latent TGF beta, thus mediating bioeffects of this cytokine. Patients with various types of systemic vasculitis (SV) showed marked TGF beta overexpression correlating with disease. Mean TGF beta 1 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 TGF beta 2 levels were not elevated. Our findings, together with other features of TGF beta's such as induction of angiogenesis and its strong chemotactic capacity, indicate that TGF beta might serve as a proinflammatory factor in SV, especially in AAV.
Kekow
J
J
Clinic of Rheumatology, Otto von Guericke University of Magdeburg, Vogelsang, Germany.
Csernok
E
E
Szymkowiak
C
C
Gross
W L
WL
D005434:Flow Cytometry; D006801:Humans; D053146:Myeloblastin; D009504:Neutrophils / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014657:Vasculitis / Q000097:blood*
D016212:Transforming Growth Factor beta; D012697:Serine Endopeptidases; D053146:Myeloblastin