Cathepsin X cleavage of the beta2 integrin regulates talin-binding and LFA-1 affinity in T cells.

T cell migration, essential for immune surveillance and response, is mediated by the integrin LFA-1. CatX, a cysteine carboxypeptidase, is involved in the regulation of T cell migration by interaction with LFA-1. We show that sequential cleavage of C-terminal amino acids from the β(2) cytoplasmic tail of LFA-1, by CatX, enhances binding of the adaptor protein talin to LFA-1 and triggers formation of the latter's high-affinity form.

DC-SIGN ligation greatly affects dendritic cell differentiation from monocytes compromising their normal function.

DC-SIGN is a C-type lectin selectively expressed by certain types of DCs, including monocyte-derived DCs. Many reports have described the impact of DC-SIGN engagement with concomitant TLR signaling in tailoring of the DC maturation process, but so far, none has addressed the importance of DC-SIGN engagement during their differentiation from blood progenitors. We therefore examined the role of DC-SIGN engagement limited to the stage of IL-4-guided differentiation of DCs from human peripheral blood monocytes but not during maturation.

γ-1-syntrophin mediates trafficking of γ-enolase towards the plasma membrane and enhances its neurotrophic activity.

Syntrophins are scaffold proteins that can bind several signaling molecules and localize them to the plasma membrane. We demonstrate here that in neuroblastoma SH-SY5Y cells, brain-specific γ1-syntrophin binds the neurotrophic factor γ-enolase through its PDZ domain, and translocates it to the plasma membrane, as shown by immunoprecipitation, surface plasmon resonance, fluorescence colocalization and flow cytometry. Extensive colocalization of γ1-syntrophin and γ-enolase was observed in neurite growth cones in differentiated SH-SY5Y cells.

Cystatin C in sera of patients with aggressive non-Hodgkin B-cell lymphoma.

Aim: To investigate the cystatin C levels in sera of patients with aggressive non-Hodgkin B-cell lymphoma.

Methods: The levels of cystatin C in sera of lymphoma patients and control group consisted of healthy individuals, were measured by using specific sandwich-type ELISA. For each patient the clinical stage of disease was determined according to Ann Arbor staging system for lymphomas.

Preparation and properties of new co-crystals of ibandronate with gluco- or galactopyranoside derivatives.

Mixtures of ibandronate monosodium salt with eleven gluco- and/or galacto-pyranoside derivatives as counterions were designed to prepare co-crystals with improved intestinal absorption. In general, gastrointestinal absorption of bisphosphonates after oral administration is approximately 1%. Co-crystals were generated by means of thermodynamically and/or kinetically controlled crystallization processes.

Mycoplasma gallisepticum and Mycoplasma synoviae express a cysteine protease CysP, which can cleave chicken IgG into Fab and Fc.

Major poultry pathogens M. gallisepticum and M. synoviae share a gene encoding a putative cysteine protease CysP similar to papain cysteine protease (C1A subfamily).

Serum cysteine proteases and their inhibitors in rheumatoid arthritis: relation to disease activity and radiographic progression.

This study aims to investigate the serum levels of cysteine proteases cathepsins B and H and their inhibitors stefin A, stefin B, and cystatin C, as well as traditional inflammatory markers such as C-reactive protein in patients with rheumatoid arthritis and to correlate these markers with scores of disease activity and radiographic progression. Seventy-two patients with rheumatoid arthritis were included from two previously described cohorts of patients with chronic polyarthritis. At inclusion, disease activity was assessed by a 28-joint count, patient global assessment, and serum C-reactive protein.

Procoagulant properties of bare and highly PEGylated vinyl-modified silica nanoparticles.

Aims: Undesired alterations of the blood clotting balance may follow the intravascular injection of nanotherapeutics/diagnostics. Here, we tested the procoagulant activity of synthetic amorphous silica (SAS) and organically modified silica (ORMOSIL) nanoparticles (NPs) and whether a high-density polyethylene glycol coating minimizes these effects.

Materials & Methods: Hageman factor- and tissue factor-dependent activation of human blood/plasma coagulation, and binding to human monocytes, endothelial cells and platelets were quantified in vitro using naked and PEGylated ORMOSIL-NPs.

The mRNA expression of pro- and anti-inflammatory cytokines in T regulatory cells in children with type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune-mediated destruction of insulin-producing beta cells in the pancreas. T regulatory cells (Tregs) represent an active mechanism of suppressing autoreactive T cells that escape central tolerance. The aim of our study was to test the hypothesis that T regulatory cells express pro- and anti-inflammatory cytokines, elements of cytotoxicity and OX40/4-1BB molecules.

[Higher percentages of T regulatory cells in children at risk for developing type 1 diabetes mellitus].

Introduction: The natural history of type 1 diabetes is concerned with the appearance of autoantibodies against antigens of pancreatic beta cells. The last decade revealed some evidence of the participation of T regulatory lymphocytes - cells which suppress immune response - in the pathogenesis of type 1 diabetes and prediabetes.

Aim Of The Study: was the assessment of T regulatory cells in the blood of children at risk for developing type 1 the diabetes mellitus.

The balance between extracellular cathepsins and cystatin C is of importance for ovarian cancer.

Background: A major step in cancer formation involves the degradation of the extracellular matrix, mediated by multiple degradative actions of (lysosomal) proteases. Extracellular release of lysosomal proteases (cathepsins) and their inhibitors has been associated with the development and progression of several types of cancer. We investigated whether cathepsins in ovarian cyst fluid (oCF) were associated with disease outcome in patients with epithelial ovarian cancer (EOC).

[The role of T-regulatory cells in the pathogenesis of immunological disturbances accompanying obesity and atherosclerosis].

Obesity and atherosclerosis, and their consequences, including cardiovascular disease, are plagues of the 21st century. Chronic inflammation, whose mechanism is not well understood, underlies the pathophysiological bases of both processes. T lymphocytes, macrophages, and the proinflammatory cytokines produced by these cells play key roles in the immunological disturbances accompanying obesity and atherosclerosis.

Cathepsins B, L and cystatin C in cyst fluid of ovarian tumors.

Introduction: In cancer, an extracellular and membrane bound localization of cathepsins contribute to the invasion of tumor cells at the basement membrane.

Methods: This is the first study that explored levels of cathepsins B (CatB), L (CatL) and their inhibitor cystatin C (CysC) in the cystic fluid (CF) of ovarian tumors (n = 110).

Results: CF contained considerable amounts of CatB, CatL and CysC.

Versatile loops in mycocypins inhibit three protease families.

Mycocypins, clitocypins and macrocypins, are cysteine protease inhibitors isolated from the mushrooms Clitocybe nebularis and Macrolepiota procera. Lack of sequence homology to other families of protease inhibitors suggested that mycocypins inhibit their target cysteine protease by a unique mechanism and that a novel fold may be found. The crystal structures of the complex of clitocypin with the papain-like cysteine protease cathepsin V and of macrocypin and clitocypin alone have revealed yet another motif of binding to papain like-cysteine proteases, which in a yet unrevealed way occludes the catalytic residue.

Cytokeratin 8 ectoplasmic domain binds urokinase-type plasminogen activator to breast tumor cells and modulates their adhesion, growth and invasiveness.

Background: Generation of plasmin is a characteristic of tumor cells, promoting the degradation of extracellular matrix, tumor progression and metastasis. The process is accelerated if plasminogen and plasminogen activator are bound to their cell surface receptors.

Results: In this study we show that the monoclonal antibody that recognizes an epitope on the cytokeratin 8 (CK8) ectoplasmic domain (anti-CK MAb) inhibits plasminogen activation mediated by urokinase-type plasminogen activator (uPA) in MCF-7 and MCF-10A neoT cells.

Equipment for neutron measurements at VR-1 Sparrow training reactor.

The VR-1 sparrow reactor is an experimental nuclear facility for training, student education and teaching purposes. The sparrow reactor is an educational platform for the basic experiments at the reactor physic and dosimetry. The aim of this article is to describe the new experimental equipment EMK310 features and possibilities for neutron detection by different gas filled detectors at VR-1 reactor.

Comparison of the effects of low intra-abdominal pressure and pentoxifylline on oxidative stress during CO2 pneumoperitoneum in rabbits.

Background: The aim of this study was to investigate the effect of low-pressure pneumoperitoneum and pentoxifylline, a methylxanthine derivative, in the prevention of injury caused by free oxygen radicals generated during CO(2 )pneumoperitoneum.

Methods: Twenty-eight rabbits were allocated randomly to 4 groups. Control group rabbits (group 1) were subjected to anesthesia for 60 min; group 2 and 3 animals were subjected to a CO(2) pneumoperitoneum (15 or 7 mm Hg); and group 4 rabbits received 50 mg/kg pentoxifylline, followed by a 15-mm-Hg pneumoperitoneum.

High expression of cathepsin B and plasminogen activator inhibitor type-1 are strong predictors of survival in glioblastomas.

In contrast to pilocytic astrocytomas (WHO grade I gliomas) that are circumscribed and cured by surgical resection, invasion is a hallmark of grades II-IV gliomas. Proteases play a major role in the invasion process and correlations between glioma grading, survival and protease expression have been demonstrated. In this study, we have chosen to study using different technical approaches (Q-RT-PCR, in situ hybridization and immunohistochemistry) the expression of five molecules involved in extracellular matrix degradation (cathepsin B, MMP2, MMP9, uPA and PAI-1) in glioblastomas in order to determine their prognostic impact among grade IV gliomas.

Cathepsin X cleaves the beta2 cytoplasmic tail of LFA-1 inducing the intermediate affinity form of LFA-1 and alpha-actinin-1 binding.

The motility of T cells depends on the dynamic spatial regulation of integrin-mediated adhesion and de-adhesion. Cathepsin X, a cysteine protease, has been shown to regulate T-cell migration by interaction with lymphocyte function associated antigen-1 (LFA-1). LFA-1 adhesion to the ICAM-1 is controlled by the association of actin-binding proteins with the cytoplasmic tail of the beta(2) chain of LFA-1.

Trypsin-specific inhibitors from the basidiomycete Clitocybe nebularis with regulatory and defensive functions.

We have isolated serine protease inhibitors from the basidiomycete Clitocybe nebularis, CnSPIs, using trypsin affinity chromatography. Full-length gene and cDNA sequences were determined for one of them, named cnispin, and the recombinant protein was expressed in Escherichia coli at high yield. The primary structure and biochemical properties of cnispin are very similar to those of the Lentinus edodes serine protease inhibitor, until now the only member of the I66 family of protease inhibitors in the MEROPS classification.

Cysteine protease-mediated cytoskeleton interactions with LFA-1 promote T-cell morphological changes.

T cells migrate through restrictive barriers in a protease-independent, amoeboid fashion that is characterized by morphological cell polarization. The interaction of cysteine-dependent carboxypeptidase cathepsin X with beta(2) integrin LFA-1 (lymphocyte function associated antigen 1) induces T-cell morphological changes, displaying into a 3D extracellular matrix a cytoplasmic projection termed a uropod. In the present study we show that inhibition of cathepsin X and a cysteine-dependent endopeptidase, cathepsin L, markedly inhibits T-cell actin polymerization, shape polarization, and chemotaxis.

Regulation of cathepsin B activity by 2A2 monoclonal antibody.

Cathepsin B (EC 3.4.22.

Cathepsin X prevents an effective immune response against Helicobacter pylori infection.

Cathepsin X, a cysteine protease, has been shown to regulate an immune response by activating beta-2 integrin receptors. In this study we demonstrate its role in regulating the immune response to infection with H. pylori.