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https://www.readbyqxmd.com/read/28445705/mutation-characterization-and-heterodimer-analysis-of-patients-with-leukocyte-adhesion-deficiency-including-one-novel-mutation
#1
Shahram Teimourian, Martin De Boer, Dirk Roos, Anna Isaian, Ehsan Moghanloo, Sharhzad Lashkary, Bita Hassani, Hasan Mollanoori, Vahid Babaei, Asaad Azarnezhad
BACKGROUND AND AIM: Leukocyte adhesion deficiency type 1 (LAD-I) is a rare, autosomal recessive disorder of neutrophil migration, characterized by severe, recurrent bacterial infections, inadequate pus formation and impaired wound healing. The ITGB2 gene encodes the β2 integrin subunit (CD18) of the leukocyte adhesion cell molecules, and mutations in this gene cause LAD-I. The aim of the current study was to investigate the mutations in patients diagnosed with LAD-I and functional studies of the impact of two previously reported and a novel mutation on the expression of the CD18/CD11a heterodimer...
April 23, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28419128/cytoskeletal-stability-and-metabolic-alterations-in-primary-human-macrophages-in-long-term-microgravity
#2
Svantje Tauber, Beatrice A Lauber, Katrin Paulsen, Liliana E Layer, Martin Lehmann, Swantje Hauschild, Naomi R Shepherd, Jennifer Polzer, Jürgen Segerer, Cora S Thiel, Oliver Ullrich
The immune system is one of the most affected systems of the human body during space flight. The cells of the immune system are exceptionally sensitive to microgravity. Thus, serious concerns arise, whether space flight associated weakening of the immune system ultimately precludes the expansion of human presence beyond the Earth's orbit. For human space flight, it is an urgent need to understand the cellular and molecular mechanisms by which altered gravity influences and changes the functions of immune cells...
2017: PloS One
https://www.readbyqxmd.com/read/28404615/myeloperoxidase-mediates-postischemic-arrhythmogenic-ventricular-remodeling
#3
Martin Mollenhauer, Kai Friedrichs, Max Lange, Jan Gesenberg, Lisa Remane, Christina Kerkenpaß, Jenny Krause, Johanna Schneider, Thorben Ravekes, Martina Maass, Marcel Halbach, Gabriel Peinkofer, Tomo Saric, Dennis Mehrkens, Matti Adam, Florian G Deuschl, Denise Lau, Birgit Geertz, Kashish Manchanda, Thomas Eschenhagen, Lukas Kubala, Tanja K Rudolph, Yuping Wu, Wh W Tang, Stanley L Hazen, Stephan Baldus, Anna Klinke, Volker Rudolph
Rationale: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase (MPO), a heme-enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. Objective: To reveal the role of MPO for the development of ventricular arrhythmias. Methods and Results: In different murine models of myocardial ischemia MPO deficiency profoundly decreased vulnerability for ventricular tachycardia (VT) upon programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry following isoproterenol injection...
April 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28399868/4-5-4-trihydroxychalcone-8-8-ethene-1-2-diyl-dinaphtalene-1-4-5-triol-and-rutin-from-gynura-segetum-inhibit-phagocytosis-lymphocyte-proliferation-cytokine-release-and-nitric-oxide-production-from-phagocytic-cells
#4
Yuandani, Ibrahim Jantan, Khairana Husain
BACKGROUND: Gynura segetum is used traditionally to treat various ailments related to the immune system, which include cancer, inflammation, rheumatism, diabetes, hypertension, and viral infections but little studies have been carried out to validate their ethnopharmacological aspects. In this study the immunosuppressive effects of G. segetum and its constituents were investigated. METHODS: Isolation of compounds from G. segetum leaves was conducted using vacuum liquid chromatography (VLC) and column chromatography (CC)...
April 11, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28396322/camp-elevating-capacity-of-the-adenylate-cyclase-toxin-hemolysin-is-sufficient-for-lung-infection-but-not-for-full-virulence-of-bordetella-pertussis
#5
Karolina Skopova, Barbora Tomalova, Ivan Kanchev, Pavel Rossmann, Martina Svedova, Irena Adkins, Ilona Bibova, Jakub Tomala, Jiri Masin, Nicole Guiso, Radim Osicka, Radislav Sedlacek, Marek Kovar, Peter Sebo
The adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) of Bordetella pertussis targets phagocytic cells expressing the complement receptor 3 (CR3, Mac-1, αMβ2 integrin or CD11b/CD18). CyaA delivers into cells an N-terminal adenylyl cyclase (AC) enzyme domain that is activated by cytosolic calmodulin and catalyzes unregulated conversion of cellular ATP into cAMP, a key second messenger subverting bactericidal activities of phagocytes. In parallel, the hemolysin (Hly) moiety of CyaA forms cation-selective hemolytic pores that permeabilize target cell membranes...
April 10, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28389621/fluid-shear-induced-cathepsin-b-release-in-the-control-of-mac1-dependent-neutrophil-adhesion
#6
Michael L Akenhead, Shunichi Fukuda, Geert W Schmid-Schönbein, Hainsworth Y Shin
There is compelling evidence that circulatory hemodynamics prevent neutrophil activation, including adhesion to microvessels, in the microcirculation. However, the underlying mechanism or mechanisms by which that mechanoregulation occurs remain unresolved. Here, we report evidence that exposure to fluid shear stress (FSS) promotes neutrophils to release cathepsin B (ctsB) and that this autocrine regulatory event is antiadhesive for neutrophils on endothelial surfaces through Mac1-selective regulation. We used a combined cell-engineering and immunocytochemistry approach to find that ctsB was capable of cleaving Mac1 integrins on neutrophils and demonstrated that this proteolysis alters their adhesive functions...
April 7, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28389358/microrna-125b-inhibits-aml-cells-differentiation-by-directly-targeting-fes
#7
Jinhang Hu, Lufeng Zheng, Xiao Shen, Yan Zhang, Cheng Li, Tao Xi
MicroRNA-125b (miR-125b) has been reported to be upregulated in several kinds of leukemia, suggesting that miR-125b plays a role in Leukemia development. In this study, it was shown that miR-125b expression level decreased in response to 1α, 25-dihydroxy-vitamin D3 (1,25D3) in a dose- and time-dependent manner and miR-125b blocked 1,25D3-induced monocytic differentiation of U937 cells. In addition, miR-125b decreased mRNA expression of myelomonocytic differentiation markers, including CD11c, CD18 and CD64 and arrested the cell cycle at the S phase in U937 and HL60 cells...
April 4, 2017: Gene
https://www.readbyqxmd.com/read/28381106/atypical-cytologic-presentation-of-a-histiocytic-sarcoma-in-a-cavalier-king-charles-spaniel-dog
#8
Lorelei L Clarke, Lisa S Kelly, Bridget Garner, Cathy A Brown
A Cavalier King Charles Spaniel dog was presented because of a 10-d history of progressive vomiting, inappetence, and lethargy, with mild neurologic signs. Fine-needle aspirates of splenic nodules seen on ultrasound were suggestive of a carcinoma. On autopsy, a disseminated neoplasm was present in the lung, spleen, and adrenal glands. Additionally, there was a Chiari-like malformation of the skull with corresponding syringomyelia of the cranial spinal cord. Histologically, the neoplasm was comprised of a pleomorphic population of round cells with a high mitotic rate...
April 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28370678/wound-healing-in-mac-1-deficient-mice
#9
Lin Chen, Sridevi Nagaraja, Jian Zhou, Yan Zhao, David Fine, Alexander Y Mitrophanov, Jaques Reifman, Luisa A DiPietro
Mac-1 (CD11b/CD18) is a macrophage receptor that plays several critical roles in macrophage recruitment and activation. Because macrophages are essential for proper wound healing, the impact of Mac-1 deficiency on wound healing is of significant interest. Prior studies have shown that Mac-1-/- mice exhibit deficits in healing, including delayed wound closure in scalp and ear wounds. The current study examined whether Mac-1 deficiency influences wound healing in small excisional and incisional skin wounds. Three millimeter diameter full thickness excisional wounds and incisional wounds were prepared on the dorsal skin of Mac-1 deficient (Mac-1 -/-) and wild type (WT) mice, and wound healing outcomes were examined...
April 1, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28368012/illuminating-dynamic-neutrophil-trans-epithelial-migration-with-micro-optical-coherence-tomography
#10
Kengyeh K Chu, Mark E Kusek, Linbo Liu, Avira Som, Lael M Yonker, Huimin Leung, Dongyao Cui, Jinhyeob Ryu, Alexander D Eaton, Guillermo J Tearney, Bryan P Hurley
A model of neutrophil migration across epithelia is desirable to interrogate the underlying mechanisms of neutrophilic breach of mucosal barriers. A co-culture system consisting of a polarized mucosal epithelium and human neutrophils can provide a versatile model of trans-epithelial migration in vitro, but observations are typically limited to quantification of migrated neutrophils by myeloperoxidase correlation, a destructive assay that precludes direct longitudinal study. Our laboratory has recently developed a new isotropic 1-μm resolution optical imaging technique termed micro-optical coherence tomography (μOCT) that enables 4D (x,y,z,t) visualization of neutrophils in the co-culture environment...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28366795/%C3%AE-2-integrins-rather-than-%C3%AE-1-integrins-mediate-alternaria-induced-ilc2-trafficking-to-the-lung
#11
Maya R Karta, Peter S Rosenthal, Andrew Beppu, Christine Y Vuong, Marina Miller, Sudipta Das, Richard C Kurten, Taylor A Doherty, David H Broide
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) expand in the lungs of mice during type 2 inflammation induced by the fungal allergen Alternaria alternata. The increase in ILC2 numbers in the lung has been largely attributed to local proliferation and whether ILC2s migrate from the circulation to the lung following Alternaria exposure is unknown. OBJECTIVE: We examined whether human (lung, lymph node, blood) and mouse lung ILC2s express β1 and β2 integrin adhesion molecules, and whether these integrins are required for trafficking of ILC2 into the lungs of mice METHODS: Human and mouse ILC2s were assessed for surface expression of β1 and β2 integrins adhesion molecules by flow cytometry...
March 30, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28343767/neural-cell-adhesion-molecule-expression-in-dilated-cardiomyopathy-is-associated-with-intramyocardial-inflammation-and-hypertrophy
#12
Karsten Ostermann, Heinz-Peter Schultheiss, Michel Noutsias
Chronic intramyocardial inflammation (inflammatory cardiomyopathy/DCMi) is linked to the pathogenesis of dilated cardiomyopathy (DCM). Neural cell adhesion molecule (NCAM) is involved in orchestrating cardiac muscle morphogenesis, but is down-regulated after embryogenesis. We investigated NCAM expression in adult DCM hearts, its possible association with DCMi-parameters, and with cardiomyocyte hypertrophy (CMH). Endomyocardial biopsies (EMBs) from DCM patients (n=85; n=37 females; age: 48±19years; LVEF <40%) and controls from non-cardiac deaths were immunostained for DCMi markers and for NCAM expression, and quantified by digital image analysis (DIA)...
March 18, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28340410/development-of-fusogenic-glass-surfaces-that-impart-spatiotemporal-control-over-macrophage-fusion-direct-visualization-of-multinucleated-giant-cell-formation
#13
James J Faust, Wayne Christenson, Kyle Doudrick, Robert Ros, Tatiana P Ugarova
Implantation of synthetic material, including vascular grafts, pacemakers, etc. results in the foreign body reaction and the formation of multinucleated giant cells (MGCs) at the exterior surface of the implant. Despite the long-standing premise that fusion of mononucleated macrophages results in the formation of MGCs, to date, no published study has shown fusion in context with living specimens. This is due to the fact that optical-quality glass, which is required for the majority of live imaging techniques, does not promote macrophage fusion...
June 2017: Biomaterials
https://www.readbyqxmd.com/read/28336558/remnant-cholesterol-elicits-arterial-wall-inflammation-and-a-multilevel-cellular-immune-response-in-humans
#14
Sophie J Bernelot Moens, Simone L Verweij, Johan G Schnitzler, Lotte C A Stiekema, Merijn Bos, Anne Langsted, Carlijn Kuijk, Siroon Bekkering, Carlijn Voermans, Hein J Verberne, Børge G Nordestgaard, Erik S G Stroes, Jeffrey Kroon
OBJECTIVE: Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). APPROACH AND RESULTS: Arterial wall inflammation and bone marrow activity were measured using (18)F-FDG PET/CT...
March 23, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28323564/differential-susceptibility-of-bighorn-sheep-ovis-canadensis-and-domestic-sheep-ovis-aries-neutrophils-to-mannheimia-haemolytica-leukotoxin-is-not-due-to-differential-expression-of-cell-surface-cd18
#15
Rohana P Dassanayake, Sudarvili Shanthalingam, Weiguo Liu, Eduardo Casas, Subramaniam Srikumaran
Bighorn sheep ( Ovis canadensis ) are more susceptible to pneumonia caused by Mannheimia haemolytica than are domestic sheep ( Ovis aries ). Leukotoxin produced by M. haemolytica is the principal virulence factor involved in pneumonia pathogenesis. Although leukotoxin is cytolytic to all subsets of ruminant leukocytes, neutrophils are the most susceptible subset. Bighorn sheep neutrophils are 4- to 8-fold more susceptible to leukotoxin-induced cytolysis than are domestic sheep neutrophils. We hypothesized that the higher susceptibility of bighorn sheep neutrophils, in comparison to domestic sheep neutrophils, is due to higher expression of CD18, the receptor for leukotoxin on leukocytes...
March 21, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28320532/atypical-histiocytosis-in-red-squirrels-sciurus-vulgaris
#16
S H Smith, K Stevenson, J Del-Pozo, S Moss, A Meredith
Four red squirrels (Sciurus vulgaris) were subjected to necropsy examination over a 3-year period as part of a broader surveillance study. The squirrels presented with cutaneous, subcutaneous and/or internal swellings and nodules that consisted microscopically of sheets of atypical round cells and multinucleated giant cells. There was moderate anisokaryosis with rare mitoses. Nuclei ranged from oval to indented or C-shaped and some were bizarre, twisted or multilobulated. Many giant cells also had a bizarre morphology, with anisokaryosis within individual cells...
March 17, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28301611/gtl001-a-bivalent-therapeutic-vaccine-against-human-papillomavirus-16-and-18-induces-antigen-specific-cd8-t-cell-responses-leading-to-tumor-regression
#17
Michaël Esquerré, Myriam Bouillette-Marussig, Anne Goubier, Marie Momot, Christophe Gonindard, Hélène Keller, Astrid Navarro, Marie-Christine Bissery
BACKGROUND: Prophylactic vaccines are available for women and girls not yet infected with HPV, but women already infected with HPV need a treatment to prevent progression to high-grade cervical lesions and cancer. GTL001 is a bivalent therapeutic vaccine for eradicating HPV-infected cells that contains HPV16 E7 and HPV18 E7 both fused to detoxified adenylate cyclase from Bordetella pertussis, which binds specifically to CD11b+ antigen-presenting cells. This study examined the ability of therapeutic vaccination with GTL001 adjuvanted with topical imiquimod cream to induce functional HPV16 E7- and HPV18 E7-specific CD8+ T cell responses...
2017: PloS One
https://www.readbyqxmd.com/read/28298656/a-high-salt-diet-enhances-leukocyte-adhesion-in-association-with-kidney-injury-in-young-dahl-salt-sensitive-rats
#18
Hidenori Takahashi, Suguru Nakagawa, Yaqiong Wu, Yukari Kawabata, Atsushi Numabe, Yasuo Yanagi, Yasuhiro Tamaki, Yoshio Uehara, Makoto Araie
Salt-sensitive hypertension is associated with severe organ damage. Generating oxygen radicals is an integral component of salt-induced kidney damage, and activated leukocytes are important in oxygen radical biosynthesis. We hypothesized that a high-salt diet causes the upregulation of immune-related mechanisms, thereby contributing to the susceptibility of Dahl salt-sensitive rats to hypertensive kidney damage. For verifying the hypothesis, we investigated leukocytes adhering to retinal vessels when Dahl salt-sensitive rats were challenged with a high-salt (8% NaCl) diet using acridine orange fluoroscopy and a scanning laser ophthalmoscope...
March 16, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28247912/net-producing-cd16-high-cd62l-dim-neutrophils-migrate-to-tumor-sites-and-predict-improved-survival-in-patients-with-hnscc
#19
Camilla Rydberg Millrud, Åsa Kågedal, Susanna Kumlien Georén, Ola Winqvist, Rolf Uddman, Ronia Razavi, Eva Munck-Wikland, Lars Olaf Cardell
The concept of functional neutrophil subsets is new and their clinical significance in malignancies is unknown. Our study investigated the role of CD16(dim) CD62L(high) , CD16(high) CD62L(high) and CD16(high) CD62L(dim) neutrophil subsets in head and neck squamous cell carcinoma (HNSCC) patients. These neutrophil subsets may play different roles in immune-related activity in cancer, based on their profile, activation state and migration ability within a tumor site, which may be important in predicting cancer prognoses...
March 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28217966/pathogenesis-of-diffuse-alveolar-hemorrhage-in-murine-lupus
#20
Haoyang Zhuang, Shuhong Han, Pui Y Lee, Ravil Khaybullin, Stepan Shumyak, Li Lu, Amina Chatha, Anan Afaneh, Yuan Zhang, Chao Xie, Dina Nacionales, Lyle Moldawer, Xin Qi, Li-Jun Yang, Westley H Reeves
OBJECTIVE: Diffuse alveolar hemorrhage (DAH) in lupus patients is >50% fatal. The cause is unknown. The pathogenesis of DAH in C57BL/6 mice with pristane-induced lupus, a model of human lupus-associated DAH, was examined. METHODS: Clinical/pathological and immunological manifestations DAH in pristane-lupus were compared with human DAH. Tissue distribution of pristane was examined by mass spectrometry. Cell types responsible for disease were determined by in vivo depletion using clodronate liposomes (CloLip) and anti-neutrophil monoclonal antibodies (GR1)...
February 19, 2017: Arthritis & Rheumatology
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