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Host-Parasite Interactions With Macrophages In Culture
Published in Hans H. Gadebusch, Phagocytes and Cellular Immunity, 2020
Lee S. F. Soderberg, Morris Solotorovsky
A third major group of lysosomal hydrolases is made up of peptide peptidohydrolases. Macrophage enzymes in this category include cathepsin D and E, BPN hydrolase, and esteroproteases. Cathepsins hydrolyze peptides, especially at bonds between an aromatic amino acid and a free α-amino group.129 At pH 3.5, all cathepsin D and 75 to 85% cathepsin E were active whereas at pH 2.0, 90% cathepsin E and only trace cathepsin D were active.130 Cathepsin D content was higher in macrophages from immunized animals than in normal macrophages.100 BPN hydrolase is a proteolytic enzyme resembling chymotrypsin. N-benzoyl-D,L-phenylalanine-β-naphthol ester (BPN) is the most commonly used substrate for assaying this enzyme. Acetyl-L-tyrosine ethyl ester and glycyl-L-phenylalanine amide are also used as substrates. BPN hydrolase is easily distinguishable from cathepsin D by its pH optimum of 5.5.24 The BPN hydrolase content is higher in macrophages from immunized animals than from normal animals.100 Elastase-like esteroproteases found in peripheral blood leukocytes were present in smaller quantities in alveolar macrophages.124 These enzymes hydrolyze certain components of connective tissue such as elastic fibers, basement membrane, and cartilage protein-polysaccharide. Macrophage lysosome preparations and whole-cell extracts were tested for ability to hydrolyze elastase substrates. Alanine-p-nitrophenylesterase activity was assayed using f-butyloxycarbonyl-L-alanine p-nitrophenol as the substrate, and the absorbence of liberated p-nitrophenol at 347.5 nm wavelength served as the index of enzyme activity. Elastolysis activity was assayed using orceinimpregnated, bovine ligamentum nuchae elastin as the substrate. Hydrolysis was determined by liberation of the orcein dye. A third, more highly specific enzyme, acetyltrialanine methyl esterase was less in evidence in macrophage granules than the other two enzymes. The substrate for this third enzyme was N-acetyl-L-analyl-L-ananyl-Lalanine methyl ester and activity was monitored as a change in pH.
Deficiency of Selected Cathepsins Does Not Affect the Inhibitory Action of ECTV on Immune Properties of Dendritic Cells
Published in Immunological Investigations, 2020
Magdalena Bossowska-Nowicka, Matylda B. Mielcarska, Justyna Struzik, Agnieszka Jackowska-Tracz, Michał Tracz, Karolina P. Gregorczyk-Zboroch, Małgorzata Gieryńska, Felix N. Toka, Lidia Szulc-Dąbrowska
Our study showed that in most cases JAWS II and GM-BM cells exhibited comparable levels of CD80 and CD86 molecules among immature and mature WT cells and cells with knockdown of CtsB, CtsL and CtsS, albeit in some cases we observed slightly, but significantly, increased expression of these molecules in cathepsin knockdown cells. However, studies regarding the influence of cathepsins on the expression of costimulatory molecules on DCs surface rule out the requirement of CtsB, CtsL and CtsS for the expression of CD80, CD86 and CD40 molecules (Gonzalez-Leal et al., 2014; Yang et al., 2005). The comparable expression of these molecules was found in Ctsb−/− Ctsl−/− and WT BMDCs among unstimulated cells and cells stimulated with LPS, L. major antigen, and killed or live L. major promastigotes (Gonzalez-Leal et al., 2014). Furthermore, levels of the activation markers CD40, CD80, CD86 in DCs from lung and the peribronchial lymph nodes were similar in Ctss−/− and WT mice following LPS exposure (Yang et al., 2005). The elevated level of CD80, CD86, and CD40 expression was observed in cathepsin E-deficient DCs compared to WT cells (Kakehashi et al., 2007).
Current Molecular and Genetic Aspects of Pancreatic Cancer, the Role of Metastasis Associated Proteins (MTA): A Review
Published in Journal of Investigative Surgery, 2018
Efstathios T. Pavlidis, Theodoros E. Pavlidis
Genetic studies indicate that pancreatic cancer originates from the three already mentioned (IPMN, MCN, PanIN) premalignant lesions [2]. The majority of them consist of pancreatic intraepithelial neoplasia (PanIN 1A, PanIN 1B, and PanIN 3) [59, 60]; however, a matter exists concerning the evolution mode. According to the research of whole genome sequences, it has been determined that different precancerous lesions are associated with specific gene mutations, which reflect on the histological type of neoplasm [61]. The latter is important since further studies on these mutations may contribute to early diagnosis at the initial stage of the disease. It has been reported that the long lasting carcinogenesis process may reach even up to 17 years; while after its completion and the first clinical manifestation of the disease, the survival time is restricted to approximately 2 years [62]. Therefore, the innovation of gene expression biomarkers is necessary for making the diagnosis at the stage of premalignant lesions [63]. Since it is rather unattainable in human tissues, the scientific research has been focused on experimental models in rats aiming for detection of reliable diagnostic biomarkers [64]. Detection of pancreatic cancer tumors and precursor lesions has been attempted in mouse models by assay of the protease cathepsin E activity (CathE). It was found to be particularly increased in pancreatic duct adenocarcinoma at an early stage [65]. These diagnostic accuracy efforts by sensitive screening tests concern first the groups of high risk and mainly the most common group of familial pancreatic cancer [66].
Downregulated Cathepsin E expression in bone marrow-derived macrophages from the pre-clinical familial amyloid polyneuropathy model
Published in Amyloid, 2019
João Moreira, Margarida Saraiva, Maria João Saraiva
Inflammation is a hallmark of several neurodegenerative disorders including familial amyloid polyneuropathy (FAP). FAP is associated with extracellular deposition of mutant transthyretin (TTR), leading to degeneration of cells and tissues, particularly in the peripheral nervous system (PNS). Cathepsin E (CtsE) is an intracellular aspartic protease of the endolysosomal pathway, with major roles in intermediation for antigen presentation and chemotaxis [1]. Taking into account that FAP patients display quantitative and qualitative abnormalities in macrophages [2], we investigated the potential role of CtsE in cells of the immune system, namely bone marrow-derived macrophages (BMDM), in a transgenic mouse model of the disease.