Basic aminopeptidase (APB) and leukotriene-a4-hydrolase (LTA4H) in the plasma, synovia and synovium of rats sensitive and insensitive to induction of arthritis by type-II collagen

Abstract

Rheumatoid arthritis is an autoimmune, inflammatory and systemic disease, which affects about 1% of the worldwide population with highest incidence in women. The progressive destruction of cartilage and bone of joints involved are the hallmarks of the disease and, moreover, there may be extra-articular involvement and occurrence of comorbidities. Several mechanisms are involved in the disease establishment and chronicicity, as the activation of macrophages, neutrophils, lymphocytes T and B and dendritic cells, formation of immune complexes, angiogenesis and release of cytokines and chemokines. The destruction of cartilage, inflammatory mechanisms and antigenic processing in this pathology could be associated to zinc metalloenzymes with anion-activated basic aminopeptidase (APB) and leukotriene-A4-hydrolase (LTA4H) activities. The present project will evaluate APB/LTA4H catalytic activities in the plasma, synovia and synovium of rats submitted to induction of arthritis by administration of type-II collagen, which developed or not the typical arthritic-induced knee inflammation, in relation to the severity of this inflammation and the levels of tumor necrosis factor-alpha (TNF-alpha) and anti-collagen type II antibodies in the plasma. The aims of this study are to show the bifunctional relationship between APB and LTA4H activities and to bring light to the etiology and development of rheumatoid arthritis and to the possible role of these enzyme activities as diagnostic markers and/or potential therapeutic targets of this pathology. (AU)