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leukocyte adhesion

Walter H Reinhart
The hematocrit (Hct) determines the oxygen carrying capacity of blood, but also increases blood viscosity and thus flow resistance. From this dual role the concept of an optimum Hct for tissue oxygenation has been derived. Viscometric studies using the ratio Hct/blood viscosity at high shear rate showed an optimum Hct of 50-60% for red blood cell (RBC) suspensions in plasma. For the perfusion of an artificial microvascular network with 5-70μm channels the optimum Hct was 60-70% for high driving pressures. With lower shear rates or driving pressures the optimum Hct shifted towards lower values...
October 21, 2016: Clinical Hemorheology and Microcirculation
Liang Gao, Gülce Sila Gülcüler, Lieke Golbach, Helena Block, Alexander Zarbock, Ana Martin-Villalba
Integrin activation is crucial for regulation of leukocyte rolling, adhesion and trans-vessel migration during inflammation and occurs by engagement of myeloid cells through factors presented by inflamed vessels. However, endothelial-dependent mechanisms of myeloid cell recruitment are not fully understood. Here we show using an autoperfused flow chamber assay of whole blood neutrophils and intravital microscopy of the inflamed cremaster muscle that CD95 mediates leukocyte slow rolling, adhesion and transmigration upon binding of CD95-ligand (CD95L) that is presented by endothelial cells...
October 20, 2016: ELife
Shanika Panagodage, Hannah E Juen Yong, Fabricio Da Silva Costa, Anthony J Borg, Bill Kalionis, Shaun P Brennecke, Padma Murthi
Preeclampsia (PE), a serious hypertensive disorder of pregnancy, remains a leading cause of perinatal morbidity and mortality worldwide. Perturbed trophoblast function and impaired placental development early in pregnancy are key features. Low-dose acetylsalicylic acid (LDA) administered before 16 weeks' gestation significantly reduces the risk for PE. However, the exact mechanisms of action of LDA, particularly on trophoblast function, are unclear. We hypothesized that LDA influences placental trophoblast function and reverses PE-associated abnormalities...
October 14, 2016: American Journal of Pathology
Anika Stadtmann, Alexander Zarbock
PURPOSE OF REVIEW: Since the discovery of the lack of kindlin-3 expression as the reason for the immunopathology leukocyte adhesion deficiency III syndrome, the role of kindlin-3 in inflammatory processes was investigated in a numerous studies. This review gives an overview about recent findings regarding the role of kindlin-3 in neutrophil activation and recruitment. RECENT FINDINGS: Kindlin-3, together with talin-1, contributes essentially to the activation of β2-integrins in neutrophils...
October 5, 2016: Current Opinion in Hematology
Alba Sulaj, Johanna Zemva, Ulrike Zech, Annika Woehning, Maik Brune, Gottfried Rudofsky, Peter P Nawroth, Thomas Fleming, Rüdiger von Bauer
BACKGROUND: The aim of this study was to investigate the effect of a lifestyle intervention in obesity on the soluble form of the activated leukocyte cell adhesion molecule (sALCAM) and its association with metabolic parameters. METHODS: Twenty-nine obese subjects selected from the OPTIFAST®52 program. This program consisted into 2 crucial phases: an initial 12-week active weight reduction phase, followed by a 40-week weight maintenance phase. At baseline, after 12 weeks and at the end of the program, fasting glucose and insulin, total cholesterol, LDL-C, HDL-C, triglycerides, adiponectin, leptin, high sensitivity CRP, sALCAM, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and leptin-to-adiponectin-ratio were determined...
October 13, 2016: BMC Endocrine Disorders
Kerstin Renner, Sonja Hellerbrand, Fabian Hermann, Christine Riedhammer, Yvonne Talke, Gabriela Schiechl, Manuel Rodriguez Gomez, Simone Kutzi, Dagmar Halbritter, Nicole Goebel, Hilke Brühl, Robert Weissert, Matthias Mack
Little is known about the role of IL-3 in multiple sclerosis (MS) in humans and in experimental autoimmune encephalomyelitis (EAE). Using myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE, we show that CD4(+) T cells are the main source of IL-3 and that cerebral IL-3 expression correlates with the influx of T cells into the brain. Blockade of IL-3 with monoclonal antibodies, analysis of IL-3 deficient mice, and adoptive transfer of leukocytes demonstrate that IL-3 plays an important role for development of clinical symptoms of EAE, for migration of leukocytes into the brain, and for cerebral expression of adhesion molecules and chemokines...
October 6, 2016: JCI Insight
Johanna M U Silvola, Helena Virtanen, Riikka Siitonen, Sanna Hellberg, Heidi Liljenbäck, Olli Metsälä, Mia Ståhle, Tiina Saanijoki, Meeri Käkelä, Harri Hakovirta, Seppo Ylä-Herttuala, Pekka Saukko, Matti Jauhiainen, Tibor Z Veres, Sirpa Jalkanen, Juhani Knuuti, Antti Saraste, Anne Roivainen
Given the important role of inflammation and the potential association of the leukocyte trafficking-associated adhesion molecule vascular adhesion protein 1 (VAP-1) with atherosclerosis, this study examined whether functional VAP-1 is expressed in atherosclerotic lesions and, if so, whether it could be targeted by positron emission tomography (PET). First, immunohistochemistry revealed that VAP-1 localized to endothelial cells of intra-plaque neovessels in human carotid endarterectomy samples from patients with recent ischemic symptoms...
October 12, 2016: Scientific Reports
Monica Baiula, Paola Galletti, Giulia Martelli, Roberto Soldati, Laura Belvisi, Monica Civera, Samantha Deianira Dattoli, Santi Mario Spampinato, Daria Giacomini
A novel series of beta-lactam derivatives that was designed and synthesized to target RGD-binding and leukocyte integrins is reported. The compound library was evaluated by investigating the effects on integrin-mediated cell adhesion and cell signaling in cell lines expressing alphaVbeta3, alphaVbeta5, alphaVbeta6, alpha5beta1, alphaIIbbeta3, alpha4beta1, and alphaLbeta2 integrins. SAR analysis of the new series of azetidinones enabled the recognition of structural elements associated with integrin selectivity...
October 11, 2016: Journal of Medicinal Chemistry
Fang Zhang, Guiyou Liu, Yali Bu, Xiaofeng Ma, Junwei Hao
For the epigenetic characterization of myasthenia gravis (MG), we determined whether long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) are expressed differentially in subjects with and without MG. Compared with healthy control subjects, the MG patients had 1561 upregulated lncRNAs, 1034 downregulated lncRNAs, 921 upregulated mRNAs, and 806 downregulated mRNAs (fold change>2.0). Several GO terms including nucleic acid transcription factor activity, inflammatory response, regulation of leukocyte activation, lymphocyte proliferation and regulation of B cell proliferation were enriched in gene lists, suggesting a potential correlation with MG...
October 15, 2016: Journal of Neuroimmunology
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
Henry Hui, Kathy A Fuller, Wendy N Erber, Matthew D Linden
Platelets are subcellular blood elements with a well-established role in haemostasis. Upon activation platelets undergo granule exocytosis, resulting in α-granule P-Selectin being expressed on the cell membrane. This allows binding of activated platelets to P-Selectin glycoprotein ligand 1 (PSGL-1) expressing leukocytes, forming leukocyte-platelet aggregates (LPAs). Whole blood flow cytometry (FCM) has demonstrated that elevated circulating LPAs (especially monocyte LPAs) are linked to atherothrombosis in high risk patients, and that activated platelet binding influences monocytes towards a pro-adhesive and pro-atherogenic phenotype...
October 5, 2016: Methods: a Companion to Methods in Enzymology
Natalie K Binder, Jemma Evans, Lois A Salamonsen, David K Gardner, Tu'uhevaha J Kaitu'u-Lino, Natalie J Hannan
Embryo implantation requires synchronized dialogue between the receptive endometrium and activated blastocyst via locally produced soluble mediators. During the mid-secretory (MS) phase of the menstrual cycle, increased glandular secretion into the uterine lumen provides important mediators that modulate the endometrium and support the conceptus during implantation. Previously we demonstrated the importance of vascular endothelial growth factor (VEGF) in the human uterus, particularly with respect to embryo implantation...
2016: PloS One
Hyun Ju Yoo, Jee-Soo Lee, Ji-Eun Kim, JaYoon Gu, Youngil Koh, Inho Kim, Hyun Kyung Kim
INTRODUCTION: When leukocytes are stimulated by reactive oxygen species (ROS), they release nuclear contents into the extracellular milieu, called by extracellular traps (ET). The nuclear contents are mainly composed of the histone-DNA complex and neutrophil elastase. This study investigated whether leukemic cells could release ET and the released histone could induce endothelial activation, eventually resulting in leukemic progression. METHODS: The circulating ET were measured in 80 patients with hematologic diseases and 40 healthy controls...
2016: PloS One
Pablo H Cutini, María B Rauschemberger, Marisa J Sandoval, Virginia L Massheimer
In this work we investigate whether, despite the procalcific action of alendronate on bone, the drug would be able to regulate in vitro the main cellular events that take part in atherosclerotic lesion generation. Using endothelial cell cultures we showed that Alendronate (1-50μM) acutely enhances nitric oxide production (10-30min). This stimulatory action of the bisphosphonate involves the participation of MAPK signaling transduction pathway. Under inflammatory stress, the drug reduces monocytes and platelets interactions with endothelial cells induced by lipopolysaccharide...
October 2, 2016: Journal of Molecular and Cellular Cardiology
Debashree Goswami, Dietmar Vestweber
The entry of leukocytes into tissues requires well-coordinated interactions between the immune cells and endothelial cells which form the inner lining of blood vessels. The molecular basis for recognition, capture, and adhesion of leukocytes to the endothelial apical surface is well studied. This review will focus on recent advances in our understanding of events following the firm interaction of leukocytes with the inner surface of the blood vessel wall. We will discuss how leukocytes initiate the transmigration (diapedesis) process, trigger the opening of gaps in the endothelial barrier, and eventually move through this boundary...
2016: F1000Research
Chin-Yi Cheng, Yu-Chen Lee
Inflammation plays a crucial role in the pathophysiology of acute ischemic stroke. In the ischemic cascade, resident microglia are rapidly activated in the brain parenchyma and subsequently trigger inflammatory mediator release, which facilitates leukocyte-endothelial cell interactions in inflammation. Activated leukocytes invade the endothelial cell junctions and destroy the blood-brain barrier integrity, leading to brain edema. Toll-like receptors (TLRs) stimulation in microglia/macrophages through the activation of intercellular signaling pathways secretes various proinflammatory cytokines and enzymes and then aggravates cerebral ischemic injury...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
R Palomba, A Parodi, M Evangelopoulos, S Acciardo, C Corbo, E de Rosa, I K Yazdi, S Scaria, R Molinaro, N E Toledano Furman, J You, M Ferrari, F Salvatore, E Tasciotti
Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV)...
October 5, 2016: Scientific Reports
Garth L Burn, Georgina H Cornish, Katarzyna Potrzebowska, Malin Samuelsson, Juliette Griffié, Sophie Minoughan, Mark Yates, George Ashdown, Nicolas Pernodet, Vicky L Morrison, Cristina Sanchez-Blanco, Harriet Purvis, Fiona Clarke, Rebecca J Brownlie, Timothy J Vyse, Rose Zamoyska, Dylan M Owen, Lena M Svensson, Andrew P Cope
Integrins are heterodimeric transmembrane proteins that play a fundamental role in the migration of leukocytes to sites of infection or injury. We found that protein tyrosine phosphatase nonreceptor type 22 (PTPN22) inhibits signaling by the integrin lymphocyte function-associated antigen-1 (LFA-1) in effector T cells. PTPN22 colocalized with its substrates at the leading edge of cells migrating on surfaces coated with the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1). Knockout or knockdown of PTPN22 or expression of the autoimmune disease-associated PTPN22-R620W variant resulted in the enhanced phosphorylation of signaling molecules downstream of integrins...
October 4, 2016: Science Signaling
Maria L Breser, Ruben D Motrich, Leonardo R Sanchez, Virginia E Rivero
BACKGROUND: Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant...
October 4, 2016: Prostate
Guo-Hua Jin, Wei Xu, Yang Shi, Li-Bo Wang
Gastric cancer (GC) is a prevalent cancer, which remains incurable, and therefore requires an alternative treatment method. Celecoxib is a nonsteroidal anti-inflammatory drug that targets cyclooxygenase-2, and exhibits anticancer effects. The present study aimed to investigate the anti-GC mechanism of celecoxib using bioinformatics methods. Gene expression datasets GSE56807 (GC tissues and normal gastric tissues) and GSE54657 (celecoxib-treated and non-treated human GC epithelial AGS cells) were downloaded from the Gene Expression Omnibus database...
October 2016: Oncology Letters
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