Abstract
Proteinase-3 (PR-3) is a neutral serine proteinase present in azurophil granules of human polymorphonuclear leukocytes and serves as the major target antigen of antineutrophil cytoplasmic antibodies with a cytoplasmic staining pattern (c-ANCA) in Wegener's granulomatosis (WG). The WG disease appears as severe vasculitis in different organs (e.g. kidney, nose and lung). Little is known about the expression and distribution of PR-3 in the lung. We found that PR-3 is expressed in normal lung tissue and is upregulated in lung tissue of patients with WG. Interestingly, the parenchymal cells (pneumocytes type I and II) and macrophages, and not the neutrophils, express PR-3 most strongly and may contribute to lung damage in patients with WG via direct interaction with antineutrophil cytoplasmic antobodies (ANCA). These findings suggest that the PR-3 expression in parenchymal cells of lung tissue could be at least one missing link in the etiopathogenesis of pulmonary pathology in ANCA-associated disease.
Highlights
Proteinase-3 (PR-3) is a 29,000 Da neutral serine proteinase stored in the azurophil granules of polymorphonuclear leukocytes [1]
PR-3 is identical to the target antigen associated with some systemic vasculitides such as Wegener’s granulomatosis (WG) and microscopic polyarteritis [8]
antineutrophil cytoplasmic antobodies (ANCA) = antineutrophil cytoplasmic antibodies; alkaline phosphatase–anti-alkaline phosphatase (APAAP) = alkaline phosphatase–antialkaline phosphatase; c-ANCA = antineutrophil cytoplasmic antibodies with a cytoplasmic staining pattern; PR-3 = proteinase-3; WG = Wegener’s granulomatosis; RT-PCR = reverse transcriptasepolymerase chain reaction
Summary
Proteinase-3 (PR-3) is a 29,000 Da neutral serine proteinase stored in the azurophil granules of polymorphonuclear leukocytes [1]. PR-3 has broad proteolytic activity and degrades a variety of extracellular matrix proteins, including fibronectin, type IV collagen and laminin [2,3]. PR-3 is identical to myeloblastin, which is a growth-promoting protein from myeloid cells [4]. PR-3 has potent antimicrobial activity both against bacteria and fungi [5,6]. PR-3 is identical to the target antigen (antineutrophil cytoplasmic antibodies with a cytoplasmic staining pattern [c-ANCA]) associated with some systemic vasculitides such as WG and microscopic polyarteritis [8]. It is not yet known whether antineutrophil cytoplasmic antibodies
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