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Impairment and Differential Expression of PR3 and MPO on Peripheral Myelomonocytic Cells with Endothelial Properties in Granulomatosis with Polyangiitis

DOI: 10.1155/2012/715049

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Background. Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune-mediated diseases characterized by vasculitic inflammation of respiratory tract and kidneys. Clinical observations indicated a strong association between disease activity and serum levels of certain types of autoantibodies (antineutrophil cytoplasm antibodies with cytoplasmic [cANCA in GPA] or perinuclear [pAN CA in MPA] immunofluorescence). Pathologically, both diseases are characterized by severe microvascular endothelial cell damage. Early endothelial outgrowth cells (eEOCs) have been shown to be critically involved in neovascularization under both physiological and pathological condition. Objectives. The principal aims of our study were (i) to analyze the regenerative activity of the eEOC system and (ii) to determine mPR3 and MPO expression in myelo monocytic cells with endothelial characteristics in GPA and MPA patients. Methods. In 27 GPA and 10 MPA patients, regenerative activity blood-derived eEOCs were analyzed using a culture-forming assay. Flk-1+, CD133+/Flk-1+, mPR3+, and Flk-1+/mPR3+ myelomonocytic cells were quantified by FACS analysis. Serum levels of Angiopoietin-1 and TNF- were measured by ELISA. Results. We found reduced eEOC regeneration, accompanied by lower serum levels of Angiopoietin-1 in GPA patients as compared to healthy controls. In addition, the total numbers of Flk-1+ myelomonocytic cells in the peripheral circulation were decreased. Membrane PR3 expression was significantly higher in total as well as in Flk-1+ myelomonocytic cells. Expression of MPO was not different between the groups. Conclusions. These data suggest impairment of the eEOC system and a possible role for PR3 in this process in patients suffering from GPA. 1. Introduction Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune diseases characterized by systemic necrotizing vasculitis mainly affecting the respiratory tract and the kidneys [1]. Histopathological analysis reveals severe structural alterations of microvascular endothelial cells, leading to impaired microcirculation in skin, joints, respiratory tract, and kidneys, respectively. Endothelial damage has been suggested to result from interactions between primed neutrophils and ANCA with the endothelium followed by endothelial detachment from the basement membrane [2]. A number of different studies showed increased levels of both, circulating mature endothelial cells and endothelial microparticles in GPA and MPA [3, 4]. Thus, patients with GPA and MPA suffer from

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