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Daniel M Vasconcelos, Raquel M Gonçalves, Catarina R Almeida, Inês O Pereira, Marta I Oliveira, Nuno Neves, Andreia M Silva, António C Ribeiro, Carla Cunha, Ana R Almeida, Cristina C Ribeiro, Ana M Gil, Elisabeth Seebach, Katharina L Kynast, Wiltrud Richter, Meriem Lamghari, Susana G Santos, Mário A Barbosa
The hypothesis behind this work is that fibrinogen (Fg), classically considered a pro-inflammatory protein, can promote bone repair/regeneration. Injury and biomaterial implantation naturally lead to an inflammatory response, which should be under control, but not necessarily minimized. Herein, porous scaffolds entirely constituted of Fg (Fg-3D) were implanted in a femoral rat bone defect and investigated at two important time points, addressing the bone regenerative process and the local and systemic immune responses, both crucial to elucidate the mechanisms of tissue remodelling...
December 2016: Biomaterials
Girlaine Pereira da Silva, Daniele Corrêa Fernandes, Mariana Vieira Vigliano, Eduardo Nunes da Fonseca, Shirley Vânia Moura Santos, Paulo Roberto Marques, Maria da Graça Justo, Kátia Costa de Carvalho Sabino, Marsen Garcia Pinto Coelho
OBJECTIVES: Echinodorus macrophyllus (Kunth) Micheli (Alismataceae) is popularly used as an infusion to treat inflammatory diseases. This work fractionated the aqueous extract of E. macrophyllus (AEEm) to improve its anti-inflammatory effects. METHODS: Aqueous extract of E. macrophyllus was fractionated by Sephadex LH-20 and analysed by HPLC-DAD. Anti-inflammatory action was evaluated, in vivo, by air pouch model (total leucocyte, protein and leukotriene B4 (LTB4 )), and, in vitro, by neutrophil migration (transwell assay) and its Mac1 expression (flow cytometry), and RAW 264...
October 10, 2016: Journal of Pharmacy and Pharmacology
Łukasz Michalak, Magdalena Bulska, Katarzyna Kudłacz, Piotr Szcześniak
Neutrophil gelatinase-associated lipocalin, known also as 24p3 lipocalin, lipocalin-2 or uterocalin (in mouse), is a small secretory protein binding small molecular weight ligands which takes part in numerous processes including apoptosis induction in leukocytes, iron transport, smell, and prostaglandins and retinol transport [19]. It was discovered in activated neutrophils as a covalent peptide associated with human gelatinase neutrophils [7]. Neutrophil lipocalin is secreted physiologically in the digestive system, respiratory tract, renal tubular cells, liver or immunity system...
January 4, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Xian M O'Brien, Jonathan S Reichner
Neutrophils are motile and responsive to tissue injury and infection. As neutrophils emigrate from the bloodstream and migrate toward a site of affliction, they encounter the tissue extracellular matrix (ECM) and thereby engage integrins. Our laboratory studies the neutrophilic response to the fungal pathogen Candida albicans either in the filamentous state of the microbe or to the purified pathogen-associated molecular pattern, β-glucan. We have gained an appreciation for the role of integrins in regulating the neutrophil anti-Candida response and how the presence or absence of ECM can drive experimental outcome...
2016: Frontiers in Immunology
Ru Li, Cordula Klockenbusch, Liwen Lin, Honghui Jiang, Shujun Lin, Juergen Kast
Physiological stimuli such as thrombin, or pathological stimuli such as lysophosphatidic acid (LPA), activate platelets. The activated platelets bind to monocytes through P-selectin-PSGL-1 interactions, but also release the contents of their granules, commonly called "platelet releasate". It is known that monocytes in contact with platelet releasate produce reactive oxygen species (ROS). Reversible cysteine oxidation by ROS is considered to be a potential regulator of protein function. In a previous study, we used THP-1 monocytic cells exposed to LPA- or thrombin-induced platelet releasate and a modified biotin switch assay to unravel the biological processes that are influenced by reversible cysteine oxidation...
October 3, 2016: Journal of Proteome Research
Marcus V Buri, Carol C Dias, Christiano M V Barbosa, Amanda Nogueira-Pedro, Antonio C Ribeiro-Filho, Antonio Miranda, Edgar J Paredes-Gamero
Due to the cytotoxic effect of antimicrobial peptides (AMP) against several microorganism and tumor cells has been proposed their association with the immune system. However, just a few reports have shown this relationship. In this study, mice were treated with gomesin, a β-hairpin AMP that exhibit high cytotoxicity against bacterial and tumor cells. Different effects in the immune system were observed, such as, decrease of CD3(+) in T lymphocytes (Control: 17.7±1.4%; Gomesin: 7.67±1.2%) and in hematopoietic progenitors and increase of hematopoietic stem cell (Control: 0...
September 7, 2016: Peptides
Y Takeda, T Kato, H Ito, Y Kurota, A Yamagishi, T Sakurai, A Araki, H Nara, N Tsuchiya, H Asao
Myeloid-derived suppressor cells (MDSCs) have a wide spectrum of immunosuppressive activity; control of these cells is a new target for improving clinical outcomes in cancer patients. MDSCs originate from unusual differentiation of neutrophils or monocytes induced by inflammatory cytokines, including granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage (GM)-CSF. However, MDSCs are difficult to detect in neutrophil or monocyte populations because they are not uniform cells, resembling both neutrophils and monocytes; thus, they exist in a heterogeneous population...
August 29, 2016: Clinical and Experimental Immunology
Christian Machacek, Verena Supper, Vladimir Leksa, Goran Mitulovic, Andreas Spittler, Karel Drbal, Miloslav Suchanek, Anna Ohradanova-Repic, Hannes Stockinger
Folate, also known as vitamin B9, is necessary for essential cellular functions such as DNA synthesis, repair, and methylation. It is supplied to the cell via several transporters and receptors, including folate receptor (FR) β, a GPI-anchored protein belonging to the folate receptor family. As FRβ shows a restricted expression to cells of myeloid origin and only a subset of activated macrophages and placental cells have been shown to express functional FRβ, it represents a promising target for future therapeutic strategies...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Mohd Hanif Zulfakar, Rebecca M Porter, Charles M Heard
Psoriasis is an incurable autoimmune disease characterized by patches of abnormal red, itchy and scaly skin. This work examined the modulation of inflammation, hyperproliferation and immune cell markers following topical application of fish oil (FO) in comparison to the antipsoriatic agents, betamethasone dipropionate (BD) and salicylic acid (SA), to GsdmA3(Dfl)/+ mice, a hair loss mutant which also exhibits epidermal hyperproliferation akin to psoriasis. The mice were dosed with 100 mg of the test formulation and after 10 days, the mice were sacrificed, skin sections excised and subjected to immunohistochemical determination of COX-2, K17 and MAC-1; and immunofluorescence of Ki-67...
August 2016: FEBS Open Bio
Yan Li, Jie Huang, Niamh M Foley, Yunyun Xu, Yi Ping Li, Jian Pan, H Paul Redmond, Jiang Huai Wang, Jian Wang
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by an excessive inflammatory response within the lungs and severely impaired gas exchange resulting from alveolar-capillary barrier disruption and pulmonary edema. The costimulatory protein B7H3 functions as both a costimulator and coinhibitor to regulate the adaptive and innate immune response, thus participating in the development of microbial sepsis and pneumococcal meningitis. However, it is unclear whether B7H3 exerts a beneficial or detrimental role during ALI...
2016: Scientific Reports
Yehonatan Pasternak, Havatzelet Yarden-Bilavsky, Yona Kodman, Meira Zoldan, Hannah Tamary, Shai Ashkenazi
OBJECTIVE: The objective was to investigate the effect of commonly used inhaled corticosteroids on white blood cell count (WBC) and to examine the mechanisms involved. METHODS: This randomized comparative study comprised 60 healthy adults. We measured the effects of budesonide (by face mask inhalation or aerosol inhaler), fluticasone (by inhaler), and saline inhalation (control) on WBC and the differential leukocyte count, especially the absolute neutrophil count (ANC)...
October 2016: American Journal of Emergency Medicine
Maria Raquel Cosate, Gabriela Hase Siqueira, Gisele Oliveira de Souza, Silvio Arruda Vasconcellos, Ana Lucia T O Nascimento
A severe re-emergingzoonosis, leptospirosis, is caused by pathogenic spirochetes of the genus Leptospira. Several studies have identified leptospiral surface proteins with the ability to bind ECM and plasma components, which could mediate adhesion and invasion through the hosts. It has been shown that Mce of pathogenic Leptospira spp. is an RGD (Arg-Gly-Asp)-motif-dependent virulence factor, responsible for infection of cells and animals. In the present article, we decided to further study the repertoire of the Mce activities in leptospiral biological properties...
September 2016: Microbiology and Immunology
Julia E Sepulveda-Diaz, Mohand O Ouidja, Sergio B Socias, Sabah Hamadat, Serge Guerreiro, Rita Raisman-Vozari, Patrick P Michel
Purified microglial cells in culture are frequently used to model brain inflammatory responses but obtaining large yields of these cells on a routine basis can be quite challenging. Here, we demonstrate that it is possible to achieve high-yield isolation of pure microglial (MAC-1(+) /Fcrls(+) /Ccr2(-) ) cells from postnatal brain tissue through a simple culture procedure that mainly relies on the adhesion preference of these cells to the polycation polyethyleneimine (PEI) in serum-supplemented DMEM medium. Accordingly, other synthetic or biological substrates failed to mimic PEI effects under the same culture conditions...
November 2016: Glia
Yao Wang, Yiyang Luo, Qiang Zhao, Zhijian Wang, Zejun Xu, Xinru Jia
G4 PAMAM dendrimer molecules were modified via covalently conjugating RGDC, RAADyC, and PEG chains on the periphery (Mac-1), by which a nanogel drug carrier with enzyme-sensitivity (NG-1) was constructed through an oxidation reaction by using NaIO4 to initiate the chemical cross-link of the functional groups on the periphery of dendrimers. Mac-1 and NG-1 both had a spherelike shape with a relatively uniform size of 20 nm for Mac-1 and 50 nm for NG-1 as evidenced by TEM, SEM, and DLS measurements. NG-1 showed much higher drug loading capacity as compared with that of Mac-1 although the cavities in the dendritic structure were used to encapsulate drug molecules as reported in many literatures...
August 10, 2016: ACS Applied Materials & Interfaces
Anna E Bortnick, Traci M Bartz, Joachim H Ix, Michel Chonchol, Alexander Reiner, Mary Cushman, David Owens, Eddy Barasch, David S Siscovick, John S Gottdiener, Jorge R Kizer
OBJECTIVE: Calcification of the aortic valve and adjacent structures involves inflammatory, lipid and mineral metabolism pathways. We hypothesised that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults. METHODS: We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of the 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate or echocardiographic data...
July 13, 2016: Heart: Official Journal of the British Cardiac Society
Grace Chen, Jungshan Chang, Dachuan Zhang, Sandra Pinho, Jung-Eun Jang, Paul S Frenette
Vaso-occlusive crisis (VOC) is one of the most common complications of sickle cell disease (SCD). Recurrent episodes of VOC may cause irreversible organ damage and early mortality in patients with SCD. Emerging evidence suggests that VOC arises from a complex cascade that involves interactions among multiple blood and endothelial cells in the vasculature. Previous studies have identified αMβ2 integrin (Mac-1) as a critical molecule that mediates heterotypic interactions between red blood cells (RBCs) and adherent leukocytes and promotes VOC in SCD mice...
October 2016: Experimental Hematology
Diana Amantea, Michelangelo Certo, Francesco Petrelli, Giacinto Bagetta
Repurposing the macrolide antibiotic azithromycin has recently been suggested as a promising neuroprotective strategy for the acute treatment of ischemic stroke. Here, we aim at further characterizing the immunomodulatory properties of intraperitoneal (i.p.) administration of this drug and, more importantly, at assessing whether neuroprotection can also be achieved by the more clinically relevant intravenous (i.v.) route of administration in a mouse model of focal cerebral ischemia induced by transient (30-min) middle cerebral artery occlusion (MCAo)...
July 8, 2016: Assay and Drug Development Technologies
Nataly P Podolnikova, Yevgeniya S Kushchayeva, YiFei Wu, James Faust, Tatiana P Ugarova
The subfamily of β2 integrins is implicated in macrophage fusion, a hallmark of chronic inflammation. Among β2 family members, integrin Mac-1 (αMβ2, CD11b/CD18) is abundantly expressed on monocyte/macrophages and mediates critical adhesive reactions of these cells. However, the role of Mac-1 in macrophage fusion leading to the formation of multinucleated giant cells remains unclear. Moreover, the role of integrin αDβ2 (CD11d/CD18), a receptor with recognition specificity overlapping that of Mac-1, is unknown...
August 2016: American Journal of Pathology
Ling-Li Guo, Su-Yang Yu, Meng Li
The aim of the present study was to explore the functions of histone acetyltransferase binding to origin recog-nition complex (ORC) 1 (HBO1) during tumor development and to screen for HBO1 inhibitors. The chromatin immuno-precipitation sequencing (ChIP-seq) data of HBO1 in the RKO human colon cancer cell line (GSE33007) were downloaded from the Gene Expression Omnibus (GEO) database. The reads were then mapped back to a reference genome hg19. The PCR duplicate reads were removed by using SAMtools software and the shift was calculated using SPP and MaSC software...
July 2016: International Journal of Molecular Medicine
Kimberly L Jordan-Williams, Neela Ramanujam, Andrew G Farr, Alanna Ruddell
Lymphocyte- and leukocyte-mediated lymph node (LN) lymphatic sinus growth (lymphangiogenesis) is involved in immune responses and in diseases including cancer and arthritis. We previously discovered a 10.1.1 Ab that recognizes the lymphatic endothelial cell (LEC) surface protein mCLCA1, which is an interacting partner for LFA1 and Mac-1 that mediates lymphocyte adhesion to LECs. Here, we show that 10.1.1 Ab treatment specifically induces LEC proliferation, and influences migration and adhesion in vitro. Functional testing by injection of mice with 10...
2016: PloS One
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