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Lin Li, Xiaotian Qi, Weili Sun, Hisham Abdel-Azim, Siyue Lou, Hong Zhu, Nemani V Prasadarao, Alice Zhou, Hiroyuki Shimada, Koichi Shudo, Yong-Mi Kim, Sajad Khazal, Qiaojun He, David Warburton, Lingtao Wu
Neutrophils generated by granulocyte colony-stimulating factor (GCSF) are functionally immature and, consequently, cannot effectively reduce infection and infection-related mortality in cancer chemotherapy-induced neutropenia (CCIN). Am80, a retinoic acid (RA) agonist that enhances granulocytic differentiation by selectively activating transcription factor RA receptor alpha (RARα), alternatively promotes RA-target gene expression. We found that in normal and malignant primary human hematopoietic specimens, Am80-GCSF combination coordinated proliferation with differentiation to develop complement receptor-3 (CR3)-dependent neutrophil innate immunity, through altering transcription of RA-target genes RARβ2, C/EBPε, CD66, CD11b, and CD18 This led to generation of functional neutrophils capable of fighting infection, whereas neutralizing neutrophil innate immunity with anti-CD18 antibody abolished neutrophil bactericidal activities induced by Am80-GCSF Further, Am80-GCSF synergy was evaluated using six different dose-schedule-infection mouse CCIN models...
October 13, 2016: EMBO Molecular Medicine
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...
October 4, 2016: Biomaterials
Md Nasimuzzaman, Danielle Lynn, Rebecca Ernst, Michele Beuerlein, Richard H Smith, Archana Shrestha, Scott Cross, Kevin Link, Carolyn Lutzko, Diana Nordling, David W Russell, Andre Larochelle, Punam Malik, Johannes C M Van der Loo
Compared to other integrating viral vectors, foamy virus (FV) vectors have distinct advantages as a gene transfer tool, including their nonpathogenicity, the ability to carry larger transgene cassettes, and increased stability of virus particles due to DNA genome formation within the virions. Proof of principle of its therapeutic utility was provided with the correction of canine leukocyte adhesion deficiency using autologous CD34(+) cells transduced with FV vector carrying the canine CD18 gene, demonstrating its long-term safety and efficacy...
2016: Molecular Therapy. Methods & Clinical Development
Guido Wabnitz, Emre Balta, Yvonne Samstag
T-cells need to be tightly regulated during their activation and effector phase to assure an appropriate defence against cancer or pathogens and - vice versa - to avoid autoimmune reactions. Regulatory signals are provided via the immune synapse between T-cells and antigen-presenting cells (APCs) or target cells. The stability and kinetics of immune synapse formation is critical for proper T-cell functions. It requires dynamic rearrangements of the actin cytoskeleton necessary for organized spatio-temporal redistribution of receptors and adhesion molecules...
September 27, 2016: Advances in Biological Regulation
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
C Damgaard, J Reinholdt, Y Palarasah, C Enevold, C Nielsen, M K Brimnes, P Holmstrup, C H Nielsen
BACKGROUND AND OBJECTIVE: The periodontal pathogen Aggregatibacter actinomycetemcomitans has been proposed as pro-atherogenic, and complement-mediated adherence to red blood cells (RBCs) may facilitate its systemic spread. We investigated the ability of four strains of A. actinomycetemcomitans with differential expression of leukotoxin A (LtxA) and fimbriae to activate complement, adhere to RBCs and elicit cytokine responses by mononuclear cells (MNCs). MATERIAL AND METHODS: Aggregatibacter actinomycetemcomitans serotype b strains HK 921, HK 1651, HK 2092 and HK 2108 were fluorescence-labeled, incubated with human whole blood cells in the presence of autologous serum, and assessed for RBC adherence by flow cytometry and for capacity to induce cytokine production by cytometric bead array analysis...
September 24, 2016: Journal of Periodontal Research
Rafeeque R Alyethodi, Umesh Singh, Sushil Kumar, Rajib Deb, Rani Alex, Sheetal Sharma, Gyanendra S Sengar, B Prakash
Fast and economical means of assaying SNP's are important in diagnostic assays, especially when a large number of animals have to be screened for a genetic disease. This study was aimed at the development of a fast and economical screening assay for bovine leukocyte adhesion deficiency (BLAD) which is an important genetic disease of cattle industry. Four primers were designed where the outer primers amplify a 354 bp amplicon of CD18 gene carrying the polymorphism responsible for BLAD. The specifically designed inner primers in conjunction with the modified reaction mixture and cyclic conditions ensured amplification of either of wild or mutated alleles...
2016: SpringerPlus
Maria E Stålhammar, Richard Sindelar, Lena Douhan Håkansson
We have previously observed that neutrophils from neonates exhibit different migratory responses to intermediate and end-target chemoattractants compared to adults. The aim of the present study was to investigate the effect of the chemoattractants IL-8 (intermediate) and formyl-methionine-leucyl-phenylalanine (fMLP; end-target) on cell surface receptor expression involved in adhesion, migration and granule release of neutrophils from term newborn infants and adults. Heparinized cord blood from 16 healthy term infants delivered by caesarean section and peripheral blood from 17 healthy adults were incubated with 1 μM IL-8 or 0...
September 8, 2016: Scandinavian Journal of Immunology
Claudia Augello, Daniele Cattaneo, Cristina Bucelli, Andrea Terrasi, Elisa Fermo, Ida Martinelli, Alessandra Iurlo, Umberto Gianelli
: Morbidity and mortality of BCR-ABL1-negative myeloproliferative neoplasm (MPN) patients are influenced by disease-related hemostatic complications, mostly of thrombotic nature. The pathogenesis of thrombosis is multifactorial: in particular, it has been demonstrated that a deregulated expression of Mac1 (also known as surface receptor integrin CD18/CD11b) by leukocytes has a role in favoring platelets' activation in MPN patients. Based on these data, we investigated the epigenetic status of CD18/CD11b in 78 primary myelofibrosis (PMF) patients to explore any possible association between the epigenetic profiles of these two genes and thrombotic risk...
September 5, 2016: Annals of Hematology
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
Anders G Kjaergaard, Anders Dige, Jeppe S Nielsen, Else Tønnesen, Jan Krog
Endothelial activation is pivotal in the development and escalation of sepsis. Central to endothelial activation is the endothelial up-regulation of cellular adhesion molecules (CAMs) including E-selectin, ICAM-1, VCAM-1, and PECAM-1. Shed CAMs are also found in circulating soluble forms (sCAMs). We investigated whether sCAMs can be used as biomarkers for the differentiation between septic and non-septic patients. Furthermore, we investigated lymphocyte and monocyte expression of LFA-1 (CD11a/CD18) and VLA-4 (CD49d/CD29) ligands for ICAM-1 and VCAM-1, respectively...
October 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
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
Michael A Grassi, Vidhya R Rao, Siquan Chen, Dingcai Cao, Xiaoyu Gao, Patricia A Cleary, R Stephanie Huang, Andrew D Paterson, Rama Natarajan, Jalees Rehman, Timothy S Kern
BACKGROUND: White blood cells have been shown in animal studies to play a central role in the pathogenesis of diabetic retinopathy. Lymphoblastoid cells are immortalized EBV-transformed primary B-cell leukocytes that have been extensively used as a model for conditions in which white blood cells play a primary role. The purpose of this study was to investigate whether lymphoblastoid cell lines, by retaining many of the key features of primary leukocytes, can be induced with glucose to demonstrate relevant biological responses to those found in diabetic retinopathy...
2016: PloS One
M Mikiewicz, I Otrocka-Domagała, K Paździor-Czapula, M Gesek
The aim of the study was the evaluation of morphology and immunophenotype of canine (19 cases) and feline (7 cases) extramedullary plasmacytomas. Tumours, located in skin, oral cavity and spleen were surgically excised, fixed and processed for histopathology and immunohistochemistry (CD79α, CD18, proliferating cell nuclear antigen, metallothionein). Histologically, tumours were classified into mature, cleaved, asynchronous, polymorphous blastic, hyalin, or monomorphous blastic type. All evaluated tumours showed cytoplasmic expression of CD79α antigen...
2016: Polish Journal of Veterinary Sciences
M Faller, C Lamm, V K Affolter, K Valerius, S Schwartz, P F Moore
OBJECTIVES: To describe a small subset of canine solitary cutaneous histiocytoma in which lymph node metastasis has been documented. METHODS: Cases of dogs with solitary cutaneous histiocytoma lesions and regional lymph node metastasis diagnosed via histopathology were found through a retrospective search of the databases of IDEXX Laboratories and the University of California, Davis Veterinary Medical Teaching Hospital Clinical Diagnostic Laboratories. Information on signalment, history and clinical follow-up was obtained from the submittal form and/or via a questionnaire to the submitting veterinarian...
October 2016: Journal of Small Animal Practice
Isaclaudia G de Azevedo-Quintanilha, Adriana Vieira-de-Abreu, André Costa Ferreira, Daniele O Nascimento, Alessandra M Siqueira, Robert A Campbell, Tatiana P Teixeira Ferreira, Tatiana M Gutierrez, Gabriel M Ribeiro, Patricia M R E Silva, Alysson R Carvalho, Patricia T Bozza, Guy A Zimmerman, Hugo C Castro-Faria-Neto
BACKGROUND: Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a potentially lethal complication of clinical malaria. Acute lung injury in MA-ARDS shares features with ARDS triggered by other causes, including alveolar inflammation and increased alveolar-capillary permeability, leading to leak of protein-rich pulmonary oedema fluid. Mechanisms and physiologic alterations in MA-ARDS can be examined in murine models of this syndrome. Integrin αDβ2 is a member of the leukocyte, or β2 (CD18), sub-family of integrins, and emerging observations indicate that it has important activities in leukocyte adhesion, accumulation and signalling...
2016: Malaria Journal
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
Xiao Na Ge, Sung Gil Ha, Yana G Greenberg, Amrita Rao, Idil Bastan, Ada G Blidner, Savita P Rao, Gabriel A Rabinovich, P Sriramarao
Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1-expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs...
August 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
Xin Liu, Junling Wang, Huiyun Zhang, Mengmeng Zhan, Hanqiu Chen, Zeman Fang, Chiyan Xu, Huifang Chen, Shaoheng He
Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection...
2016: Mediators of Inflammation
Charles P Semba, Thomas R Gadek
Dry eye disease (DED) is a multifactorial disorder of the ocular surface characterized by symptoms of discomfort, decreased tear quality, and chronic inflammation that affects an estimated 20 million patients in the US alone. DED is associated with localized inflammation of the ocular surface and periocular tissues leading to homing and activation of T cells, cytokine release, and development of hyperosmolar tears. This inflammatory milieu results in symptoms of eye dryness and discomfort. Homing of T cells to the ocular surface is influenced by the binding of lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18; αLβ2), a cell surface adhesion protein, to its cognate ligand, intercellular adhesion molecule-1 (ICAM-1; CD54), which is expressed on inflamed ocular/periocular epithelium and vascular endothelium...
2016: Clinical Ophthalmology
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