Neutral aminopeptidase and dipeptidyl peptidase IV in the development of collagen II-induced arthritis

This study evaluated the hypothesis that neutral (APN) and dipeptidyl-IV (DPPIV) aminopeptidase activity levels would be critical for the susceptibility to arthritis in collagen-induced model (CIA). The macroscopic signs of arthritis in CIA rats were checked and peripheral blood, synovial fluid and synovial tissue from knee joint were withdrawn. Soluble (SF) and solubilized membrane-bound (MF) fractions from the synovial tissue and peripheral blood mononuclear cells (PBMCs) were obtained. APN and DPPIV activities were fluorometrically quantified. Severe swelling in both the entire hind paws was the minimum criterion to select CIA rats with arthritis. These arthritic rats had high APN in plasma, synovial fluid and SF of the synovial tissue, together with low APN and DPPIV in MF of PBMCs and hallmark histological changes in tibio-tarsal joint. CIA rats with no macroscopic signs of arthritis were diagnosed as resistant and they had low APN in MF of the synovial tissue, low DPPIV in SF of PBMCs and high DPPIV in plasma together with histological aspects of tibio-tarsal joint similar to healthy control rats. Data suggested that APN and DPPIV activity levels are related to the development of arthritis, being protective or inducer of the susceptibility. Understanding what is controlling the compartment-specific changes of these peptidases and looking at ways in which to manipulate their activities may lead to a better knowledge of the arthritic processes and novel treatments.

Basic aminopeptidase activity is an emerging biomarker in collagen-inducedrheumatoid arthritis

The objective of this study was to investigate the catalytic activity of basic aminopeptidase (APB) and itsassociation with periarticular edema and circulating tumor necrosis factor (TNF)-alpha and type II collagen(CII) antibodies (AACII) in a rat model of rheumatoid arthritis (RA) induced by CII (CIA). Edema does not occurin part of CII-treated, even when AACII is higher than in control. TNF-alpha is detectable only in edematousCII-treated. APB in synovial membrane is predominantly a membrane-bound activity also present in solubleform and with higher activity in edematous than in non-edematous CII-treated or control. Synovial fluid andblood plasma have lower APB in non-edematous than in edematous CII-treated or control. In peripheral bloodmononuclear cells (PBMCs) the highest levels of APB are found in soluble form in control and in membraneboundform in non-edematous CII-treated. CII treatment distinguishes two categories of rats: one with arthritic edema, high AACII, detectable TNF-alpha, high soluble and membrane-bound APB in synovial membrane and low APB in the soluble fraction of PBMCs, and another without edema and with high AACII,undetectable TNF-alpha, low APB in the synovial fluid and blood plasma and high APB in the membranebound fraction of PBMCs. Data suggest that APB and CIA are strongly related.