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Alborz Karimzadeh, Vanessa M Scarfone, Erika Varady, Connie Chao, Karin Grathwohl, John W Fathman, David A Fruman, Thomas Serwold, Matthew A Inlay
Hematopoietic stem cells (HSCs) are the self-renewing multipotent progenitors to all blood cell types. Identification and isolation of HSCs for study has depended on the expression of combinations of surface markers on HSCs that reliably distinguish them from other cell types. However, the increasing number of markers required to isolate HSCs has made it tedious, expensive, and difficult for newcomers, suggesting the need for a simpler panel of HSC markers. We previously showed that phenotypic HSCs could be separated based on expression of CD11a and that only the CD11a negative fraction contained true HSCs...
March 15, 2018: Stem Cells Translational Medicine
Matthew Wiest, Katherine Upchurch, Wenjie Yin, Jerome Ellis, Yaming Xue, Bobby Lanier, Mark Millard, HyeMee Joo, SangKon Oh
Background: T cells play a central role in chronic inflammation in asthma. However, the roles of individual subsets of T cells in the pathology of asthma in patients remain to be better understood. Methods: We investigated the potential signatures of T cell subset phenotypes in asthma using fresh whole blood from adult atopic asthma patients (n = 43) and non-asthmatic control subjects (n = 22). We further assessed their potential clinical implications by correlating asthma severity...
2018: Allergy, Asthma, and Clinical Immunology
Eanna P Connaughton, Serika Naicker, Shirley A Hanley, Stephanie M Slevin, John K Eykelenboom, Noel F Lowndes, Timothy O'Brien, Rhodri Ceredig, Matthew D Griffin, Michael C Dennedy
Human blood monocytes are sub-classified as classical, intermediate and non-classical. In this study, it was shown that conventionally-defined human intermediate monocytes (IM) can be divided into two distinct subpopulations with mid- and high-level surface expression of HLA-DR (referred to as DRmid and DRhi IM). These IM subpopulations were phenotypically and functionally characterized in healthy adult blood by flow cytometry, migration assays and lipoprotein uptake assays. Their absolute numbers and proportions were then compared in blood samples from obese and non-obese adults...
March 5, 2018: Immunology and Cell Biology
Go Kamoshida, Takane Kikuchi-Ueda, Satoshi Nishida, Shigeru Tansho-Nagakawa, Tsuneyuki Ubagai, Yasuo Ono
Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs), has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation...
2018: Frontiers in Immunology
Gil Redelman-Sidi, Olivier Michielin, Carlos Cervera, Camillo Ribi, José María Aguado, Mario Fernández-Ruiz, Oriol Manuel
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3-targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 7, 2018: Clinical Microbiology and Infection
Carmen A Sautter, Gaël Auray, Sylvie Python, Artur Summerfield
Considering that macrophage functions are strongly impacted by the local tissue environment and the type of immune response, the aim of this study was to carefully set the methodological baseline for phenotype and functions of polarized porcine monocyte-derived macrophages. To this end, macrophages were generated in autologous serum alone or with colony-stimulating factor (CSF)-1 or CSF-2, and subsequently polarized with interferon (IFN)γ, interleukin-4 or IFNβ. IFNγ promoted expression of MHC class I, MHC class II, CD11a, and CD40 as well as LPS-induced IL-6 and IL-12...
January 30, 2018: Developmental and Comparative Immunology
Michelle D Warthan, Sonya L Washington, Samone E Franzese, Ronald M Ramus, Kyu-Rae Kim, Timothy P York, Efstratios Stratikos, Jerome F Strauss, Eun D Lee
Gestational choriocarcinomas are derived from placental trophoblast cells, with HLA-C being the only class I polymorphic molecule expressed. However, choriocarcinomas have not been profiled for endoplasmic reticulum aminopeptidase 2 (ERAP2) expression. ERAP2 trims peptides presented by human leukocyte antigens (HLA) have shown to modulate immune response. Over 50% of choriocacinomas we screened lack ERAP2 expression, which suggests the absence of ERAP2 expression allows immune evasion of choriocarcinoma cells...
January 9, 2018: Biology of Reproduction
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
Peter E Feist, Elizabeth A Loughran, M Sharon Stack, Amanda B Hummon
Cancer metastasis risk increases in older individuals, but the mechanisms for this risk increase are unclear. Many peritoneal cancers, including ovarian cancer, preferentially metastasize to peritoneal fat depots. However, there is a dearth of studies exploring aged peritoneal adipose tissue in the context of cancer. Because adipose tissue produces signals which influence several diseases including cancer, proteomics of adipose tissue in aged and young mice may provide insight into metastatic mechanisms. We analyzed mesenteric, omental, and uterine adipose tissue groups from the peritoneal cavities of young and aged C57BL/6J mouse cohorts with a low-fraction SDS-PAGE gelLC-MS/MS method...
December 27, 2017: Analytical and Bioanalytical Chemistry
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
Carmen Schröck, Carina Eydt, Florian Geburek, Lena Kaiser, Felicitas Päbst, Janina Burk, Christiane Pfarrer, Carsten Staszyk
Allogeneic equine multipotent mesenchymal stromal cells (eMSCs) have been proposed for use in regenerative therapies in veterinary medicine. A source of allogeneic eMSCs might be the bone marrow from euthanized horses. The purpose of this study was to compare in vitro characteristics of equine bone marrow derived eMSC (eBM-MSCs) from euthanized horses (eut-MSCs) and from narcotized horses (nar-MSCs). Eut-MSCs and nar-MSCs showed typical eMSC marker profiles (positive: CD44, CD90; negative: CD11a/CD18 and MHCII) and possessed tri-lineage differentiation characteristics...
November 2017: Veterinary Medicine and Science
Shin-Ichiroh Saitoh, Fumiko Abe, Atsuo Kanno, Natsuko Tanimura, Yoshiko Mori Saitoh, Ryutaro Fukui, Takuma Shibata, Katsuaki Sato, Takeshi Ichinohe, Mayumi Hayashi, Kazuishi Kubota, Hiroko Kozuka-Hata, Masaaki Oyama, Yorifumi Kikko, Toshiaki Katada, Kenji Kontani, Kensuke Miyake
Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC-pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7(+) lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7...
November 17, 2017: Nature Communications
Martha M C Elwenspoek, Xenia Hengesch, Fleur A D Leenen, Anna Schritz, Krystel Sias, Violetta K Schaan, Sophie B Mériaux, Stephanie Schmitz, Fanny Bonnemberger, Hartmut Schächinger, Claus Vögele, Jonathan D Turner, Claude P Muller
Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA ( n = 42) and those without a history of ELA (control, n = 73)...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Caleb D Swaim, Ariella F Scott, Larissa A Canadeo, Jon M Huibregtse
ISG15 is a ubiquitin-like protein that functions in innate immunity both as an intracellular protein modifier and as an extracellular signaling molecule that stimulates IFN-γ secretion. The extracellular function, important for resistance to mycobacterial disease, has remained biochemically uncharacterized. We have established an NK-92 cell-based assay for IFN-γ release, identified residues critical for ISG15 signaling, and identified the cell surface receptor as LFA-1 (CD11a/CD18; αLβ2 integrin). LFA-1 inhibition blocked IFN-γ secretion, splenocytes from CD11a-/- mice did not respond to ISG15, and ISG15 bound directly to the αI domain of CD11a in vitro...
November 2, 2017: Molecular Cell
Manuel Reina, Enric Espel
The lymphocyte function-associated antigen-1 (LFA-1) (also known as CD11a/CD18 and αL β₂), is just one of many integrins in the human body, but its significance is derived from its exclusive presence in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (or CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1...
November 3, 2017: Cancers
Elizabeth Gensterblum, Paul Renauer, Patrick Coit, Faith M Strickland, Nathan C Kilian, Shaylynn Miller, Mikhail Ognenovski, Jonathan D Wren, Pei-Suen Tsou, Emily E Lewis, Kathleen Maksimowicz-McKinnon, W Joseph McCune, Bruce C Richardson, Amr H Sawalha
OBJECTIVE: The goal of this study was to comprehensively characterize CD4+CD28+ T cells overexpressing CD11a and KIR genes, and examine the relationship between this T cell subset, genetic risk, and disease activity in lupus. METHODS: The size of the CD4+CD28+KIR+CD11a(hi) T cell subset was determined by flow cytometry, and total genetic risk for lupus was calculated in 105 female patients using 43 confirmed genetic susceptibility loci. Primary CD4+CD28+KIR+CD11a(hi) T cells were isolated from lupus patients or were induced from healthy individuals using 5-azacytidine...
October 20, 2017: Journal of Autoimmunity
Mahmoud M Elnaggar, Gaber S Abdellrazeq, Stephanie K Venn-Watson, Eric D Jensen, Victoria Hulubei, Lindsay M Fry, Randy E Sacco, William C Davis
The slow progress in understanding immunotoxic effects of environmental contaminants and their influence on disease susceptibility in whales is largely due to the limited information available on the immune systems and immune function of species included in the Cetancodontamorpha clade. Studies in species in the other major clades included in the Artiodactylamorpha, Ruminantiamorpha, Suinamorpha, and Camelidamorpha have revealed the immune systems are similar, but not identical. The present study was undertaken to expand the available monoclonal antibody reagents needed to gain insight into the composition, function, and evolution of the immune system in Cetancodontamorpha, using the dolphin (Tursiops truncatus) as a model cetacean species...
October 2017: Veterinary Immunology and Immunopathology
Cássia Mariana Bronzon da Costa, Marina Del Vecchio Filipin, Fabrícia Helena Santello, Luiz Miguel Pereira, Miriam Paula Alonso Toldo, José Clóvis do Prado Júnior, Ana Amélia Carraro Abrahão
Chagas disease afflicts 7 to 8 million people worldwide and congenital Chagas' disease usually leads to changes in the maternal environment, culminating in fetal adaptations. Several articles have described the importance of micronutrients on pregnancy, which is sensitive to infections. In Trypanosoma cruzi endemic regions, the Chagas disease is aggravated by the lack of micronutrients in an average diet, to which pregnant women are more susceptible. The aim of this study was to evaluate distinct T cells phenotypes and intracellular cytokines by flow cytometry in pregnant Wistar rats under zinc therapy during experimental Chagas' disease...
October 12, 2017: European Journal of Pharmaceutical Sciences
Tara Capece, Brandon L Walling, Kihong Lim, Kyun-Do Kim, Seyeon Bae, Hung-Li Chung, David J Topham, Minsoo Kim
The integrin lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is a key T cell adhesion receptor that mediates stable interactions with antigen-presenting cell (APC), as well as chemokine-mediated migration. Using our newly generated CD11a-mYFP knock-in mice, we discovered that naive CD8+ T cells reserve a significant intracellular pool of LFA-1 in the uropod during migration. Intracellular LFA-1 quickly translocated to the cell surface with antigenic stimulus. Importantly, the redistribution of intracellular LFA-1 at the contact with APC was maintained during cell division and led to an unequal inheritance of LFA-1 in divided T cells...
November 6, 2017: Journal of Cell Biology
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