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https://www.readbyqxmd.com/read/30105030/azithromycin-clears-bordetella-pertussis-infection-in-mice-but-also-modulates-innate-and-adaptive-immune-responses-and-t-cell-memory
#1
Lisa Borkner, Alicja Misiak, Mieszko M Wilk, Kingston H G Mills
Treatment with the macrolide antibiotic azithromycin (AZM) is an important intervention for controlling infection of children with Bordetella pertussis and as a prophylaxis for preventing transmission to family members. However, antibiotics are known to have immunomodulatory effects independent of their antimicrobial activity. Here, we used a mouse model to examine the effects of AZM treatment on clearance of B. pertussis and induction of innate and adaptive immunity. We found that treatment of mice with AZM either 7 or 14 days post challenge effectively cleared the bacteria from the lungs...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30061889/identification-of-human-b-1-helper-t-cells-with-a-th1-like-memory-phenotype-and-high-integrin-cd49d-expression
#2
Jae-Ghi Lee, Joon Young Jang, Taishi Fang, Yixuan Xu, Ji-Jing Yan, Jung-Hwa Ryu, Hee Jung Jeon, Tai Yeon Koo, Dong Ki Kim, Kook-Hwan Oh, Tae Jin Kim, Jaeseok Yang
Human B-1 cells have been proposed to be CD20+ CD27+ CD43+ CD1c- B cells found in the umbilical cord and adult peripheral blood, but their regulatory mechanisms have not been well elucidated. Previously, we reported that mouse CD49dhigh CD4+ T cells could enhance the secretion of natural antibodies by B-1 cells. In this study, we aimed to investigate the presence and helper functions of the human equivalents of murine CD49dhigh CD4+ T cells. Here, we showed that human CD49dhigh CD4+ T cells found in the peritoneal cavity (PEC), spleen, and peripheral blood can enhance the production of IgM antibodies by B-1 cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30050529/immune-cell-profiling-during-switching-from-natalizumab-to-fingolimod-reveals-differential-effects-on-systemic-immune-regulatory-networks-and-on-trafficking-of-non-t-cell-populations-into-the-cerebrospinal-fluid-results-from-the-tofingo-successor-study
#3
Lisa Lohmann, Claudia Janoschka, Andreas Schulte-Mecklenbeck, Svenja Klinsing, Lucienne Kirstein, Uta Hanning, Timo Wirth, Tilman Schneider-Hohendorf, Nicholas Schwab, Catharina C Gross, Maria Eveslage, Sven G Meuth, Heinz Wiendl, Luisa Klotz
Leukocyte sequestration is an established therapeutic concept in multiple sclerosis (MS) as represented by the trafficking drugs natalizumab (NAT) and fingolimod (FTY). However, the precise consequences of targeting immune cell trafficking for immunoregulatory network functions are only incompletely understood. In the present study, we performed an in-depth longitudinal characterization of functional and phenotypic immune signatures in peripheral blood (PB) and cerebrospinal fluid (CSF) of 15 MS patients during switching from long-term NAT to FTY treatment after a defined 8-week washout period within a clinical trial (ToFingo successor study; ClinicalTrials...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30007855/in-depth-phenotypic-characterization-of-reticulocyte-maturation-using-mass-cytometry
#4
Richard Thomson-Luque, Chengqi Wang, Francis B Ntumngia, Shulin Xu, Karoly Szekeres, Amy Conway, Swamy Rakesh Adapa, Samantha J Barnes, John H Adams, Rays H Y Jiang
Progress towards an in-depth understanding of the final steps of the erythroid lineage development is paramount for many hematological diseases. We have characterized the final stages of reticulocyte maturation from bone marrow to peripheral blood using for the first time single-cell Mass Cytometry (CyTOF). We were able to measure the expression of 31 surface markers within a single red blood cell (RBC). We demonstrate the validity of CyTOF for RBC phenotyping by confirming the progressive reduction of transferrin receptor 1 (CD71) during reticulocyte maturation to mature RBC...
July 4, 2018: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29978459/the-dual-inhibitor-of-the-phosphoinositol-3-and-pim-kinases-ibl-202-is-effective-against-chronic-lymphocytic-leukaemia-cells-under-conditions-that-mimic-the-hypoxic-tumour-microenvironment
#5
Kyle Crassini, Yandong Shen, Michael O'Dwyer, Michael O'Neill, Richard Christopherson, Stephen Mulligan, O Giles Best
Despite significant advances in treatment, chronic lymphocytic leukaemia (CLL) remains an incurable disease. Ibrutinib and idelalisib, which inhibit Bruton Tyrosine kinase (BTK) and phosphoinositol-3 (PI3) kinase-δ respectively, have become important treatment options for the disease and demonstrate the potential of targeting components of the B-cell receptor-signalling pathway. IBL-202 is a dual inhibitor of the PIM and PI3 kinases. Synergy between the pan-PIM inhibitor, pPIMi, and idelalisib against a range of haematological cell lines and primary CLL cells supports the rationale for preclinical studies of IBL-202 in CLL...
July 5, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29959213/combination-treatment-of-vla-4-targeted-radionuclide-therapy-and-immunotherapy-in-a-mouse-model-of-melanoma
#6
Jaeyeon Choi, Wissam Beaino, Ronald Fecek, Kellsye Fabian, Charles M Laymon, Brenda Kurland, Walter Storkus, Carolyn J Anderson
Very late antigen-4 (VLA-4; also known as integrin α4β1) is expressed at high levels in aggressive and metastatic melanoma tumors and may provide an ideal target for imaging and targeted radiotherapy. 177 Lu-DOTA-PEG4-LLP2A (177 Lu-LLP2A) shows high affinity for VLA-4 and had high uptake in B16F10 mouse melanoma tumors in vivo. Here, we report efficacy studies of 177 Lu-LLP2A, alone and combined with immune checkpoint inhibitors (ICI) in B16F10 tumor-bearing mice. Methods: B16F10 tumor cells (1 x 106) were implanted subcutaneously in C57BL/6 mice...
June 29, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29955944/in-contrast-to-high-cd49d-low-cxcr4-expression-indicates-the-dependency-of-chronic-lymphocytic-leukemia-cll-cells-on-the-microenvironment
#7
Csilla Kriston, Márk Plander, Ágnes Márk, Anna Sebestyén, Edina Bugyik, András Matolcsy, Gábor Barna
CD49d and CXCR4 are key determinants of interactions between chronic lymphocytic leukemia (CLL) tumor cells and their microenvironment. In this study, we investigated the effect of CD49d and CXCR4 expressions on survival of CLL cells. Primary CLL cells were cultured with CD49d ligand, VCAM-1, or bone marrow stromal cells (BMSCs); then, apoptosis and immunophenotype analyses were performed. VCAM-1 treatment could not induce direct apoptosis protection or immunophenotype change on the CD49d-expressing CLL cells, but resulted in actin reorganization...
June 28, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29921311/adipose-derived-and-bone-marrow-mesenchymal-stem-cells-a-donor-matched-comparison
#8
Samih Mohamed-Ahmed, Inge Fristad, Stein Atle Lie, Salwa Suliman, Kamal Mustafa, Hallvard Vindenes, Shaza B Idris
BACKGROUND: Adipose-derived stem cells (ASCs) have been introduced as an alternative to bone marrow mesenchymal stem cells (BMSCs) for cell-based therapy. However, different studies comparing ASCs and BMSCs have shown conflicting results. In fact, harvesting ASCs and BMSCs from different individuals might influence the results, making comparison difficult. Therefore, this study aimed to characterize donor-matched ASCs and BMSCs in order to investigate proliferation, differentiation potential and possible effects of donor variation on these mesenchymal stem cells (MSCs)...
June 19, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29776451/myeloid-specific-tak1-deletion-results-in-reduced-brain-monocyte-infiltration-and-improved-outcomes-after-stroke
#9
Anjali Chauhan, Jacob Hudobenko, Abdullah Al Mamun, Edward C Koellhoffer, Anthony Patrizz, Rodney M Ritzel, Bhanu P Ganesh, Louise D McCullough
BACKGROUND: Activation of transforming growth factor-β-activated kinase 1 (TAK1) occurs after stroke and leads to an exacerbation of brain injury. TAK1 is involved in innate and adaptive immune responses, but it has divergent inflammatory effects that are dependent on the cell type in which it is activated. There is a robust infiltration of myeloid cells after stroke; however, the contribution of myeloid TAK1 to cerebral ischemia is currently unknown. We hypothesized that myeloid-specific deletion of TAK1 would protect against ischemic brain injury...
May 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29768259/precise-intradermal-injection-of-nanofat-derived-stromal-cells-combined-with-platelet-rich-fibrin-improves-the-efficacy-of-facial-skin-rejuvenation
#10
Zhi-Jie Liang, Xiang Lu, De-Quan Li, Yi-Dan Liang, Dan-Dan Zhu, Fang-Xiao Wu, Xiao-Lin Yi, Ning He, Yan-Qing Huang, Chao Tang, Hong-Mian Li
BACKGROUND/AIMS: The rejuvenation properties of nanofat grafting have been described in recent years. However, it is not clear whether the clinical efficacy of the procedure is attributable to stem cells or linked to other components of adipose tissue. In this study we isolated nanofat-derived stem cells (NFSCs) to observe their biological characteristics and evaluate the efficacy of precise intradermal injection of nanofat combined with platelet-rich fibrin (PRF) in patients undergoing facial rejuvenation treatment...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29748447/morphological-immunophenotypic-and-genetic-features-of-chronic-lymphocytic-leukemia-with-trisomy-12-a-comprehensive-review
#11
REVIEW
Francesco Autore, Paolo Strati, Luca Laurenti, Alessandra Ferrajoli
Chronic lymphocytic leukemia is an extremely heterogeneous disease and prognostic factors such as chromosomal abnormalities are important predictors of time to first treatment and survival. Trisomy 12 is the second most frequent aberration detected by fluorescence in situ hybridization at the time of diagnosis (10-25%), and it confers an intermediate prognostic risk, with a median time to first treatment of 33 months and a median overall survival of 114 months. Here, we review the unique morphological, immunophenotypic, and genetic characteristics of patients with chronic lymphocytic leukemia and trisomy 12...
June 2018: Haematologica
https://www.readbyqxmd.com/read/29705268/aberrant-determination-of-phenotypic-markers-in-chronic-lymphocytic-leukemia-cll-lymphocytes-after-cryopreservation
#12
Lauren A Thurgood, Karen M Lower, Cindy Macardle, Bryone J Kuss
The cryopreservation of peripheral blood mononuclear cells (PBMCs) is a routine research laboratory process, enabling long-term storage of primary patient blood samples. Retrospective analysis of these samples has the potential to identify markers that may be associated with prognosis and response to treatment. To draw valid biological conclusions from this type of analysis, it is essential to ensure that any observed changes are directly related to the pathology of the disease rather than the preservation process itself...
July 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29672587/functional-relevance-of-in-vivo-half-antibody-exchange-of-an-igg4-therapeutic-antibody-drug-conjugate
#13
Peter Herbener, Kurt Schönfeld, Martin König, Matthias Germer, Jude M Przyborski, Katrin Bernöster, Jörg Schüttrumpf
An increasing number of monoclonal antibodies and derivatives such as antibody-drug conjugates (ADC) are of the IgG1 and IgG4 isotype with distinct structural and functional properties. In cases where antibody-mediated cytotoxicity is not desired, IgG4 is often used, as its Fc region is relatively poor at inducing antibody-dependent cell-mediated or complement-dependent cytotoxicity. IgG4 ADCs with highly cytotoxic drugs against proliferating target cells but which lack or have diminished antibody effector functions against quiescent cells may have a favorable safety profile compared to IgG1...
2018: PloS One
https://www.readbyqxmd.com/read/29348537/radionuclides-transform-chemotherapeutics-into-phototherapeutics-for-precise-treatment-of-disseminated-cancer
#14
Nalinikanth Kotagiri, Matthew L Cooper, Michael Rettig, Christopher Egbulefu, Julie Prior, Grace Cui, Partha Karmakar, Mingzhou Zhou, Xiaoxia Yang, Gail Sudlow, Lynne Marsala, Chantiya Chanswangphuwana, Lan Lu, LeMoyne Habimana-Griffin, Monica Shokeen, Xinming Xu, Katherine Weilbaecher, Michael Tomasson, Gregory Lanza, John F DiPersio, Samuel Achilefu
Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly in a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment of disseminated cancer by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and a contact-facilitated nanomicelle technology enabled highly selective delivery and co-localization of titanocene and radiolabelled fluorodeoxyglucose in disseminated multiple myeloma cells...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29334431/activation-state-of-circulating-eosinophils-in-nasal-polyposis
#15
Vincent Dupuch, Arlette Tridon, Sylvie Ughetto, Stéphane Walrand, Benjamin Bonnet, Claude Dubray, Aude Virlogeux, Marie-Paule Vasson, Nicolas Saroul, Thierry Mom, Laurent Gilain, Bertrand Evrard
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease with an uncertain pathophysiology. It is characterized by polyps rich in eosinophils, with an activation status already investigated at the tissue level. In a group of CRSwNP patients, we assessed the activation status of circulating eosinophils in the blood before migration into tissues. METHODS: Thirteen patients with CRSwNP and 16 healthy volunteers were enrolled. Several biologic parameters were studied: blood count of eosinophils; plasma eosinophil cationic protein; oxidative metabolism by chemiluminescence at baseline or when activated by phorbol 12-myristate 13-acetate or platelet-activating factor, with or without interleukin-5 (IL-5); percent of granulosar cells; and mean fluorescence intensity (MFI) by flow cytometry...
May 2018: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/29302252/serosal-cavities-contain-two-populations-of-innate-like-integrin-%C3%AE-4-high-cd4-t-cells-integrin-%C3%AE-4%C3%AE-1-%C3%AE-6%C3%AE-1-%C3%AE-4%C3%AE-7-and-%C3%AE-4%C3%AE-1-%C3%AE-6%C3%AE-1-%C3%AE-4%C3%AE-7-cells
#16
Jeong In Yang, Chanho Park, Inseong Kho, Sujin Lee, Kyung-Suk Suh, Tae Jin Kim
We previously reported peritoneal innate-like integrin α4 (CD49d)high CD4+ T cells that provided help for B-1a cells. Here we analyzed the expression of various integrin chains on the peritoneal and pleural integrin α4high CD4+ T cells and investigated the functional heterogeneity of the subpopulations based on the integrin expression. Pleural cavity contained a lower ratio of integrin α4high CD4+ T cells to integrin α4low CD4+ T cells than peritoneal cavity, but the pleural integrin α4high CD4+ T cells have the same characteristics of the peritoneal integrin α4high CD4+ T cells...
December 2017: Immune Network
https://www.readbyqxmd.com/read/29301866/functional-and-clinical-relevance-of-vla-4-cd49d-cd29-in-ibrutinib-treated-chronic-lymphocytic-leukemia
#17
Erika Tissino, Dania Benedetti, Sarah E M Herman, Elisa Ten Hacken, Inhye E Ahn, Kari G Chaffee, Francesca Maria Rossi, Michele Dal Bo, Pietro Bulian, Riccardo Bomben, Elisabeth Bayer, Andrea Härzschel, Julia Christine Gutjahr, Massimiliano Postorino, Enrico Santinelli, Ayed Ayed, Francesco Zaja, Annalisa Chiarenza, Gabriele Pozzato, Alexandre Chigaev, Larry A Sklar, Jan A Burger, Alessandra Ferrajoli, Tait D Shanafelt, Adrian Wiestner, Giovanni Del Poeta, Tanja Nicole Hartmann, Valter Gattei, Antonella Zucchetto
The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells...
February 5, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29233180/distinct-cytokine-patterns-may-regulate-the-severity-of-neonatal-asphyxia-an-observational-study
#18
Anna Bajnok, László Berta, Csaba Orbán, Gábor Veres, Dénes Zádori, Hajnalka Barta, Ünőke Méder, László Vécsei, Tivadar Tulassay, Miklós Szabó, Gergely Toldi
BACKGROUND: Neuroinflammation and a systemic inflammatory reaction are important features of perinatal asphyxia. Neuroinflammation may have dual aspects being a hindrance, but also a significant help in the recovery of the CNS. We aimed to assess intracellular cytokine levels of T-lymphocytes and plasma cytokine levels in moderate and severe asphyxia in order to identify players of the inflammatory response that may influence patient outcome. METHODS: We analyzed the data of 28 term neonates requiring moderate systemic hypothermia in a single-center observational study...
December 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29222169/nanoscale-tuning-of-vcam-1-determines-vla-4-dependent-melanoma-cell-plasticity-on-rgd-motifs
#19
Katharina Amschler, Eugen Kossmann, Luise Erpenbeck, Sebastian Kruss, Tillmann Schill, Margarete Schön, Sigrid M C Möckel, Joachim P Spatz, Michael P Schön
The biophysical fine-tuning of cancer cell plasticity is crucial for tumor progression but remains largely enigmatic. Although vascular cell adhesion molecule-1 (VCAM-1/CD106) has been implicated in melanoma progression, here its presentation on endothelial cells was associated with diminished melanoma cell spreading. Using a specific nanoscale modulation of VCAM-1 (tunable from 70 to 670 ligands/μm²) next to integrin ligands (RGD motifs) in a bifunctional system, reciprocal regulation of integrin α4 (ITGA4/VLA-4/CD49d)-dependent adhesion and spreading of melanoma cells was found...
March 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29213290/effect-of-isolation-technique-and-location-on-the-phenotype-of-human-corneal-stroma-derived-cells
#20
Richárd Nagymihály, Zoltán Veréb, Andrea Facskó, Morten C Moe, Goran Petrovski
Purpose: To determine the effect of the isolation technique and location upon the phenotype of human corneal stroma-derived cells (CSCs). Methods: CSCs were isolated from the corneal stroma center and periphery using the explant or enzymatic digestion technique. The native tissue was stained for functional markers, while cultured cells were analysed by FACS. PCR was used to determine gene expression in the cultured versus native cells. Results: The native stroma was positive for α -actinin, ALDH1A1, CD31, CD34, Collagen I, and Vimentin...
2017: Stem Cells International
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