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Domenico Umberto De Rose, Silvia Giliani, Lucia Dora Notarangelo, Vassilios Lougaris, Arnalda Lanfranchi, Daniele Moratto, Baldassarre Martire, Fernando Specchia, Alberto Tommasini, Alessandro Plebani, Raffaele Badolato
Leukocyte Adhesion Deficiency type 1 (LAD-1) is a rare primary immunodeficiency due to mutations in the gene encoding for the common β-chain of the β2 integrin family (CD18). Herein, we describe clinical manifestations and long-term complications of eight LAD-1 patients. Four LAD-1 patients were treated with hematopoietic stem cell transplantation (HSCT), while the remaining four, including two with moderate LAD-1 deficiency, received continuous antibiotic prophylaxis. Untreated patients presented numerous infections and autoimmune manifestations...
March 13, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Valeryi K Lishko, Valentin P Yakubenko, Tatiana P Ugarova, Nataly P Podolnikova
Platelet Factor 4 (PF4) is one of the most abundant cationic proteins secreted from α-granules of activated platelets. Based on its structure, PF4 was assigned to the CXC family of chemokines and has been shown to have numerous effects on myeloid leukocytes. However, the receptor for PF4 remains unknown. Here, we demonstrate that PF4 induces leukocyte responses through the integrin Mac-1 (αM β2 , CD11b/CD18). Human neutrophils, monocytes, U937 monocytic and HEK293 cells expressing Mac-1 strongly adhered to immobilized PF4 in a concentration-dependent manner...
March 14, 2018: Journal of Biological Chemistry
Marilia Takada, Maciej Parys, Emmalena Gregory-Bryson, Paulo Vilar Saavedra, Matti Kiupel, Vilma Yuzbasiyan-Gurkan
BACKGROUND: Histiocytic sarcoma is a rare disorder in humans, however it is seen with appreciable frequency in certain breeds of dogs, such as Bernese mountain dog. The purpose of this study was to fully characterize a novel canine histiocytic sarcoma cell line, and utilize it as a tool to screen for potential therapeutic drugs. METHODS: The histiocytic sarcoma cell line was characterized by expression of cellular markers as determined by immunohistochemistry and flow cytometry techniques...
March 1, 2018: BMC Cancer
Tommaso Neri, Valentina Scalise, Ilaria Passalacqua, Ilaria Giusti, Stefania Lombardi, Cristina Balia, Delfo D'Alessandro, Stefano Berrettini, Roberto Pedrinelli, Pierluigi Paggiaro, Vincenza Dolo, Alessandro Celi
Extracellular vesicles are submicron vesicles that upregulate the synthesis of proinflammatory mediators by lung epithelial cells. We investigated whether these structures adhere to lung epithelial cells, and whether adhesion is a prerequisite for their proinflammatory activity. Extracellular vesicles were generated by stimulation of normal human mononuclear cells with the calcium ionophore A23187, and labelled with carboxyfluorescein diacetate succinimidyl ester. Adhesion of vesicles to monolayers of immortalized bronchial epithelial (16HBE) and alveolar (A549) cells was analysed by fluorescence microscopy...
February 21, 2018: Experimental Cell Research
Edward F Plow, Yunmei Wang, Daniel I Simon
Current antithrombotic drugs, including widely used antiplatelet agents and anticoagulants, are associated with significant bleeding risk, which increases morbidity and mortality. Nevertheless, there is emerging experimental evidence that suggests that the molecular and cellular mechanisms of hemostasis and thrombosis can be separated, thereby raising the possibility of new antithrombotic therapeutic targets with reduced bleeding risk. We summarize some recently emerging examples of agents with antithrombotic activities that seem to spare hemostasis...
February 21, 2018: Blood
Sugandha Saxena, Yuri Hayashi, Lingyun Wu, Mohammad Awaji, Pranita Atri, Michelle L Varney, Abhilasha Purohit, Satyanarayana Rachagani, Surinder K Batra, Rakesh K Singh
Semaphorin-5A (SEMA5A) has differential cell surface expression between normal and cancer cells and represents an attractive target for therapeutic intervention in pancreatic cancer (PC). In this study, we delineated the pathological expression and significance of SEMA5A during PC progression and metastasis. We utilized human tissue microarrays and different PC mouse models (Pdx1-cre; LSL- Kras(G12D) , Pdx1-Cre; LSL-Kras(G12D) ; LSL-p53(R172H) and RIP1-Tag2) to analyze SEMA5A expression during PC progression...
January 19, 2018: Oncotarget
Dorota Szpak, Lahoucine Izem, Dmitriy Verbovetskiy, Dmitry A Soloviev, Valentin P Yakubenko, Elzbieta Pluskota
Atherosclerosis is a complex inflammatory process characterized by monocyte recruitment into the arterial wall, their differentiation into macrophages, and lipid accumulation. Because integrin αM β2 (CD11b/CD18) mediates multiple diverse functions of leukocytes, we examined its role in atherogenesis. αM -/- /ApoE-/- and ApoE-/- mice were fed a control or high fat diet for 3 or 16 wk to induce atherogenesis. Unexpectedly, αM deficiency accelerated development of atherosclerosis in female but not in male mice...
February 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Beth M French, Selin Sendil, Krishna Mohan Sepuru, Jolene Ranek, Lars Burdorf, Donald Harris, Emily Redding, Xiangfei Cheng, Christopher T Laird, Yuming Zhao, Benjamin Cerel, Krishna Rajarathnam, Richard N Pierson, Agnes M Azimzadeh
BACKGROUND: Human neutrophils are sequestered by pig lung xenografts within minutes during ex vivo perfusion. This phenomenon is not prevented by pig genetic modifications that remove xeno-antigens or added human regulatory molecules intended to down-regulate activation of complement and coagulation pathways. This study investigated whether recipient and donor interleukin-8 (IL-8), a chemokine known to attract and activate neutrophils during inflammation, is elaborated in the context of xenogeneic injury, and whether human or pig IL-8 promote the adhesion of human neutrophils in in vitro xenograft models...
February 9, 2018: Xenotransplantation
Michael Keck, Roelof Maarten van Dijk, Cornelia A Deeg, Katharina Kistler, Andreas Walker, Eva-Lotta von Rüden, Vera Russmann, Stefanie M Hauck, Heidrun Potschka
Information about epileptogenesis-associated changes in protein expression patterns is of particular interest for future selection of target and biomarker candidates. Bioinformatic analysis of proteomic data sets can increase our knowledge about molecular alterations characterizing the different phases of epilepsy development following an initial epileptogenic insult. Here, we report findings from a focused analysis of proteomic data obtained for the hippocampus and parahippocampal cortex samples collected during the early post-insult phase, latency phase, and chronic phase of a rat model of epileptogenesis...
April 2018: Neurobiology of Disease
Paola Monti, Darren Barnes, Anna M Adrian, Roberta Rasotto
A 4-year-old Irish Setter was presented with a history of progressive left pelvic limb lameness. Orthopedic examination revealed pain on manipulation of the left stifle. Radiographs showed an osteolytic lesion in the subchondral bone of the medial tibial condyle. Fine-needle aspirates were taken, and cytology revealed numerous cohesive clusters of plump, oval to spindloid cells often with perivascular distribution and moderate cellular atypia. A diagnosis of sarcoma was made with synovial cell sarcoma (SCS) and histiocytic sarcoma being the 2 main differentials...
February 6, 2018: Veterinary Clinical Pathology
Solange Dos Santos Costa, Márcia Cristina Fornazim, Alexandre Eduardo Nowill, Selma Giorgio
Manipulation of costimulatory and surface molecules that shape the extent of immune responses by Leishmania is suggested as one of the mechanisms of evading the host's defenses. The experiments reported here were designed to evaluate the expression of CD11b, CD11c, CD14, CD18, CD54, CD80, CD86, CD206, MHC class II and TLR-2 (Toll-like receptor 2) in human macrophages infected with L. amazonensis. Phenotypic evaluation revealed a negative modulation in CD11b, CD11c, CD14, CD18, CD54 and MHC class II molecules, depending on the level of infection...
January 30, 2018: Parasite Immunology
Sehar Nigar, Ejaz Ahmed Khan, Tahir Aziz Ahmad
Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency disorder with autosomal recessive inheritance which is characterized by presence of a defect of phagocytic function resulting from a lack of leukocyte cell surface expression of b2 integrin molecules (CD11 and CD18) that are essential for chemotaxis. The classic symptoms of the disease are failure of separation of the umbilical cord and recurrent bacterial infections, which continue throughout life. We describe here two cases of infants who presented with characteristic history of recurrent infections, delayed separation of umbilical cord and marked leukocytosis...
January 2018: JPMA. the Journal of the Pakistan Medical Association
Alissa Bally, Karelma Frontera Acevedo, Indira Pargass, Lana Gyan, Stacy Rajh, Rod Suepaul
An 8-year-old male (neutered) Labrador with a history of erythematous skin lesions and exercise intolerance for a prolonged period was suddenly found dead. Necropsy findings revealed an infiltrative, focally extensive mass which occupied 25% of the cardiac interventricular septum. Severe endocardiosis was also found on the bicuspid and tricuspid valves. The submandibular lymph nodes and kidneys were bilaterally enlarged, and the pre-hepatic lymph node and spleen were also enlarged. Multiple dermal pustules were present around the mouth and on the ear, and small ulcers were present on the tongue...
January 20, 2018: Veterinary Sciences
Navid Dashti, Mahdi Mahmoudi, Farhad Gharibdoost, Hoda Kavosi, Ramazan Rezaei, Vahideh Imeni, Ahmadreza Jamshidi, Saeed Aslani, Shayan Mostafaei, Mohammad Vodjgani
Systemic sclerosis (SSc), an autoimmune disease of connective tissue, is characterized by inflammation, fibrosis, and vessel endothelial damage. Products of Integrin subunit beta 2 (ITGB2) and selectin L (SELL) genes participate in several functional pathways of immune system. The aim of this investigation was to survey the transcript level of ITGB2 and SELL genes as well as methylation status of CpG sites in promoter region of differently expressed gene in PBMCs of SSc patients. PBMCs were isolated from whole blood of 50 SSc patients and 30 healthy controls...
January 22, 2018: Rheumatology International
A García-Salido, A Serrano-González, A M de Azagra-Garde, M Nieto-Moro, G J Melen, M Ramírez-Orellana
No abstract text is available yet for this article.
December 26, 2017: Medicina Intensiva
Liusong Yang, Lina Wang, Canjun Zhu, Junguo Wu, Yexian Yuan, Lulu Yu, Yaqiong Xu, Jingren Xu, Tao Wang, Zhengrui Liao, Songbo Wang, Xiaotong Zhu, Ping Gao, Yongliang Zhang, Xiuqi Wang, Qingyan Jiang, Gang Shu
Laminarin, a type of β-glucan isolated from brown seaweeds, exhibits verity of physiological activities, which include immunology modulation and antitumor function. To investigate the effect of laminarin on energy homeostasis, mice were orally administrated with laminarin to test food intake, fat deposition, and glucose homeostasis. Chronically, laminarin treatment significantly decreases high-fat-diet-induced body weight gain and fat deposition and reduces blood glucose level and glucose tolerance. Acutely, laminarin enhances serum glucagon-like peptide-1 (GLP-1) content and the mRNA expression level of proglucagon and prohormone convertase 1 in ileum...
November 21, 2017: Oncotarget
E de Graauw, C Sitaru, M P Horn, L Borradori, S Yousefi, D Simon, H-U Simon
BACKGROUND: Lesions of bullous pemphigoid (BP), an autoimmune subepidermal blistering disease characterized by the presence of tissue-bound and circulating autoantibodies to hemidesmosomal antigens, harbor a mixed inflammatory cellular infiltrate. In various models, neutrophils, eosinophils, mast cells, monocytes as well as B and T cells have been shown to be involved in the pathogenesis of BP. However, their interactions with and effective role in blister formation remain uncertain. This study was aimed at investigating the effect of monocyte/neutrophil interaction on blister formation in an ex vivo BP model...
December 8, 2017: Allergy
Aitor Benedicto, Joana Marquez, Alba Herrero, Elvira Olaso, Elzbieta Kolaczkowska, Beatriz Arteta
BACKGROUND: Lymphocyte Function-Associated Antigen-1 (LFA-1; CD18/CD11a) is one of the main adhesion molecules used by immune cells to infiltrate the liver under inflammatory conditions. Recently, the expression of this integrin has also been reported on several solid tumors, including colorectal cancer. However, its functional role in the metastatic progression to the liver remains unknown. Using in vitro assays and an experimental orthotopic in vivo model of liver metastasis, we aimed to elucidate the role of tumor LFA-1 in the metastatic progression by means of the partial depletion of the β2 subunit of LFA-1, required for integrin activation, firm adhesion and signaling...
December 6, 2017: BMC Cancer
Huiyun Zhang, Junling Wang, Ling Wang, Mengmeng Zhan, Shigang Li, Zeman Fang, Ciyan Xu, Yanshan Zheng, Shaoheng He
BACKGROUND AND PURPOSE: Chymase is a unique, abundant secretory product of mast cells and a potent chemoattractant for eosinophils, monocytes and neutrophils, but little is known of its influence on mast cell accumulation. EXPERIMENTAL APPROACH: A mouse peritoneal inflammation model, cell migration assay and flowcytometry analysis, were used to investigate the role of chymase in recruiting mast cells. KEY RESULTS: Chymase increased, by up to 5...
February 2018: British Journal of Pharmacology
Simone L Verweij, Raphaël Duivenvoorden, Lotte C A Stiekema, Nick S Nurmohamed, Fleur M van der Valk, Miranda Versloot, Hein J Verberne, Erik S G Stroes, Matthias Nahrendorf, Siroon Bekkering, Sophie J Bernelot Moens
Aims: Circulating monocytes infiltrate the plaque and differentiate into macrophages, contributing to an inflammatory environment which is associated with higher risk of cardiovascular events. Although the pivotal role of circulating monocytes in plaque inflammation has been firmly established, the search continues to identify specific monocyte subsets that may be especially atherogenic. Therefore, we evaluated the relation between monocyte phenotype, particularly surface receptor expression, and arterial wall inflammation in patients at increased cardiovascular risk...
March 1, 2018: Cardiovascular Research
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