Yamasaki Simone Cristina, Murari-do-Nascimento Stephanie, Silveira Paulo Flavio
Laboratory of Pharmacology, Instituto Butantan, Av. Vital Brasil, 1500, 05503-900 São Paulo, SP, Brazil.
Regul Pept. 2012 Jan 10;173(1-3):47-54. doi: 10.1016/j.regpep.2011.09.004. Epub 2011 Oct 6.
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of arthritis in CIA rats were checked and peripheral blood, synovial fluid and synovial tissue from knee joint were withdrawn.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.
在胶原诱导的关节炎模型（CIA）中，中性（APN）和二肽基肽酶-IV（DPPIV）氨肽酶活性水平对于关节炎易感性至关重要。检查了CIA大鼠的关节炎宏观体征，并采集了膝关节的外周血、滑液和滑膜组织。从滑膜组织和外周血单核细胞（PBMC）中获得了可溶性（SF）和可溶解的膜结合（MF）部分。通过荧光法对APN和DPPIV活性进行了定量分析。整个后爪严重肿胀是选择患有关节炎的CIA大鼠的最低标准。这些患有关节炎的大鼠在血浆、滑液和滑膜组织的SF中具有高APN，同时在PBMC的MF中具有低APN和DPPIV，并且胫跗关节有典型的组织学变化。没有关节炎宏观体征的CIA大鼠被诊断为抗性大鼠，它们在滑膜组织的MF中具有低APN，在PBMC的SF中具有低DPPIV，在血浆中具有高DPPIV，并且胫跗关节的组织学特征与健康对照大鼠相似。数据表明，APN和DPPIV活性水平与关节炎的发展相关，是易感性的保护因素或诱导因素。了解是什么控制了这些肽酶的特定区域变化，并寻找操纵其活性的方法，可能会更好地了解关节炎的发病过程并开发新的治疗方法。
