Research Topics
Genomes and Genes
| Ronen AlonSummaryAffiliation: Weizmann Institute of Science Country: Israel Publications
| Collaborators
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Detail Information
Publications
Right on the spot. Chemokine triggering of integrin-mediated arrest of rolling leukocytesCarlo Laudanna
Department of Pathology, University of Verona, Italy
Thromb Haemost 95:5-11. 2006....
A crosstalk between intracellular CXCR7 and CXCR4 involved in rapid CXCL12-triggered integrin activation but not in chemokine-triggered motility of human T lymphocytes and CD34+ cellsTanja Nicole Hartmann
The Weizmann Institute of Science, Rehovot, 76100, Israel
J Leukoc Biol 84:1130-40. 2008..Our findings suggest that although CXCR7 is not an intrinsic signaling receptor for CXCL12 on lymphocytes or CD34(+) cells, its blocking can be useful for therapeutic interference with CXCR4-mediated activation of integrins...
Chemokine-triggered leukocyte arrest: force-regulated bi-directional integrin activation in quantal adhesive contactsRonen Alon
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Curr Opin Cell Biol 24:670-6. 2012....
Cells on the run: shear-regulated integrin activation in leukocyte rolling and arrest on endothelial cellsRonen Alon
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Curr Opin Cell Biol 20:525-32. 2008..Different leukocyte subsets appear to use different modalities of integrin activation during rolling and arrest at distinct endothelial sites...
Chemokine signaling to lymphocyte integrins under shear flowRonen Alon
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Microcirculation 16:3-16. 2009..In this article, we present an overview of both early and recent shear-flow studies of integrin activation in lymphocytes and discuss future perspectives of integrin activation research in vitro and in vivo...
Chemokine arrest signals to leukocyte integrins trigger bi-directional-occupancy of individual heterodimers by extracellular and cytoplasmic ligandsRonen Alon
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Cell Adh Migr 4:211-4. 2010....
Force as a facilitator of integrin conformational changes during leukocyte arrest on blood vessels and antigen-presenting cellsRonen Alon
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Immunity 26:17-27. 2007..Evidence suggests that preformed cytoskeletal anchorage rather than free integrin mobility is key for force-enhanced integrin activation by chemokines and TCR signals...
Trapped versus soluble chemokines: functions in leukocyte adhesion and motilityRonen Alon
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
Immunity 33:654-6. 2010..2010) provide in vivo evidence that heparan sulfate glycosaminoglycans (GAGs) are indispensable for immobilization and function of major chemokines required for leukocyte adhesion to and crossing through blood and lymphatic vessels...
Alpha4beta1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the alpha4-cytoplasmic domainRonen Alon
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
J Cell Biol 171:1073-84. 2005....
Chemokine triggered integrin activation and actin remodeling events guiding lymphocyte migration across vascular barriersRonen Alon
Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100 Israel
Exp Cell Res 317:632-41. 2011..We will review here major findings and open questions related to these sequential guiding activities of endothelial presented chemokines, focusing mainly on lymphocyte-endothelial interactions as a paradigm for other leukocytes...
Kindlin-3 is required for the stabilization of TCR-stimulated LFA-1:ICAM-1 bonds critical for lymphocyte arrest and spreading on dendritic cellsSara W Feigelson
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Blood 117:7042-52. 2011..We suggest that Kindlin-3 selectively contributes to a final TCR-triggered outside-in stabilization of bonds generated between chemokine-primed LFA-1 molecules and cell-surface ICAM-1...
Chemokine stimulation of lymphocyte alpha 4 integrin avidity but not of leukocyte function-associated antigen-1 avidity to endothelial ligands under shear flow requires cholesterol membrane raftsRevital Shamri
Department of Immunology, Weizmann Institute of Science, Rehovot, 76100 Israel
J Biol Chem 277:40027-35. 2002..Our results provide the first evidence that a particular chemokine/GPCR pair can activate different integrins on the same cell using distinct G(i) protein-associated machineries segregated within defined membrane compartments...
Membranal cholesterol is not required for L-selectin adhesiveness in primary lymphocytes but controls a chemokine-induced destabilization of L-selectin rolling adhesionsOren Dwir
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
J Immunol 179:1030-8. 2007..Thus, the regulation of L-selectin by cholesterol-enriched microdomains varies with the cell type as well as with the identity of the destabilizing chemokine...
Talin 1 and paxillin facilitate distinct steps in rapid VLA-4-mediated adhesion strengthening to vascular cell adhesion molecule 1Eugenia Manevich
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
J Biol Chem 282:25338-48. 2007....
Loss of Kindlin-3 in LAD-III eliminates LFA-1 but not VLA-4 adhesiveness developed under shear flow conditionsEugenia Manevich-Mendelson
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Blood 114:2344-53. 2009..Deletion of the putative beta(1) Kindlin-3 binding site also retained VLA-4 adhesiveness. Thus, our study provides the first evidence that Kindlin-3 is more critical to LFA-1 than to VLA-4-adhesive functions in human lymphocytes...
Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokinesRevital Shamri
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Nat Immunol 6:497-506. 2005..These data show that chemokine-triggered lymphocyte adhesiveness involves a previously unrecognized extension step that primes LFA-1 for ligand binding and firm adhesion...
Enzymatically quiescent heparanase augments T cell interactions with VCAM-1 and extracellular matrix components under versatile dynamic contextsIlya Sotnikov
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
J Immunol 172:5185-93. 2004..These findings add another dimension to the known versatility of heparanase as a key regulator of T cell activities during inflammation, both in the context of the vasculature and at extravascular sites...
A novel genetic leukocyte adhesion deficiency in subsecond triggering of integrin avidity by endothelial chemokines results in impaired leukocyte arrest on vascular endothelium under shear flowRonen Alon
Department of Immunology, The Weizmann Institute of Science Rehovot, Israel
Blood 101:4437-45. 2003..This syndrome is the first example of a human integrin-activation deficiency associated with defective GPCR stimulation of integrin avidity at subsecond contacts, a key step in leukocyte arrest on vascular endothelium under shear flow...
RhoA is involved in LFA-1 extension triggered by CXCL12 but not in a novel outside-in LFA-1 activation facilitated by CXCL9Ronit Pasvolsky
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
J Immunol 180:2815-23. 2008....
Avidity enhancement of L-selectin bonds by flow: shear-promoted rotation of leukocytes turn labile bonds into functional tethersOren Dwir
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
J Cell Biol 163:649-59. 2003..L-selectin tethers appear adapted to undergo rapid avidity enhancement by cellular transport, a specialized mechanism not used by any other known adhesion receptor...
Talin1 is required for integrin-dependent B lymphocyte homing to lymph nodes and the bone marrow but not for follicular B-cell maturation in the spleenEugenia Manevich-Mendelson
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Blood 116:5907-18. 2010....
Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forcesEilon Woolf
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
Nat Immunol 8:1076-85. 2007..Thus, lymph node chemokines that promote motility and strongly activate lymphocyte integrins under shear forces fail to stimulate stable integrin adhesiveness in extravascular shear-free environments...
Lymphocyte crawling and transendothelial migration require chemokine triggering of high-affinity LFA-1 integrinZiv Shulman
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
Immunity 30:384-96. 2009..We propose that shear forces exerted on HA-LFA-1 trigger adhesive and invasive filopodia at apical endothelial surfaces and thereby promote lymphocyte crawling and probing for TEM sites...
DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migrationZiv Shulman
Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100, Israel
Blood 108:2150-8. 2006....
Pathways implicated in stem cell migration: the SDF-1/CXCR4 axisYaron Vagima
Immunology Department, The Weizmann Institute of Science, Rehovot, Israel
Methods Mol Biol 750:277-89. 2011..Finally, other stem cell features such as stem cell survival and proliferation, are also dependent on the SDF-1/CXCR4 axis...
Anti-inflammatory effects of an inflammatory chemokine: CCL2 inhibits lymphocyte homing by modulation of CCL21-triggered integrin-mediated adhesionsLiat Flaishon
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Blood 112:5016-25. 2008..Thus, pM levels of circulating CCL2 can exert global suppressive effects on T-cell trafficking and differentiation within peripheral lymph nodes, and may be clinically beneficial as an anti-inflammatory agent...
Occupancy of lymphocyte LFA-1 by surface-immobilized ICAM-1 is critical for TCR- but not for chemokine-triggered LFA-1 conversion to an open headpiece high-affinity stateSara W Feigelson
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
J Immunol 185:7394-404. 2010....
LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bondsTatsuo Kinashi
Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100, Israel
Blood 103:1033-6. 2004..This is a first report of an inherited Rap1 activation defect associated with a pathologic disorder in leukocyte integrin function, we herein term it "LAD-III."..
Atypical PKC-zeta regulates SDF-1-mediated migration and development of human CD34+ progenitor cellsIsabelle Petit
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
J Clin Invest 115:168-76. 2005..Our results demonstrate a central role for PKC-zeta in SDF-1-dependent regulation of hematopoietic stem and progenitor cell motility and development...
The CD81 tetraspanin facilitates instantaneous leukocyte VLA-4 adhesion strengthening to vascular cell adhesion molecule 1 (VCAM-1) under shear flowSara W Feigelson
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel 76100
J Biol Chem 278:51203-12. 2003....
Transendothelial migration of lymphocytes mediated by intraendothelial vesicle stores rather than by extracellular chemokine depotsZiv Shulman
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Nat Immunol 13:67-76. 2012..Thus, effector T lymphocytes can cross inflamed barriers through contact-guided consumption of intraendothelial chemokines without surface-deposited chemokines or extraendothelial chemokine gradients...
Real-time analysis of integrin-dependent transendothelial migration and integrin-independent interstitial motility of leukocytesZiv Shulman
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Methods Mol Biol 757:31-45. 2012..Following fixation, subcellular changes in the distribution of integrin subsets and of specific integrin-associated adaptors can be further dissected by immunofluorescence tools and by ultrastructural electron microscopic analysis...
From rolling to arrest on blood vessels: leukocyte tap dancing on endothelial integrin ligands and chemokines at sub-second contactsRonen Alon
Department of Immunology, Weizmann Institute of Science, Rehovot, 76100 Israel
Semin Immunol 14:93-104. 2002..We discuss potential regulatory mechanisms by which a given set of chemokine receptors and integrins may interact to rapidly generate high avidity, shear-resistant integrin-mediated leukocyte arrest on vascular endothelium...
Chemoattractant signals and beta 2 integrin occupancy at apical endothelial contacts combine with shear stress signals to promote transendothelial neutrophil migrationGuy Cinamon
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
J Immunol 173:7282-91. 2004....
Chapter 14. Real-time in vitro assays for studying the role of chemokines in lymphocyte transendothelial migration under physiologic flow conditionsZiv Shulman
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Methods Enzymol 461:311-32. 2009..After fixation, subcellular changes in the redistribution of these key molecules can be further dissected by immunofluorescence tools and by ultrastructural analysis based on scanning and transmission electron microscopy...
CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrowAbraham Avigdor
Immunology Department, The Weizmann Institute of Science, Rehovot, Israel
Blood 103:2981-9. 2004..Taken together, our data suggest a key role for CD44 and HA in SDF-1-dependent transendothelial migration of HSCs/HPCs and their final anchorage within specific niches of the BM...
Real-time in vitro assay for studying chemoattractant-triggered leukocyte transendothelial migration under physiological flow conditionsGuy Cinamon
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Methods Mol Biol 239:233-42. 2004
Chemokine induction of integrin adhesiveness on rolling and arrested leukocytes local signaling events or global stepwise activation?Ronen Alon
Department of Immunology, Weizmann Institute of Science, Rehovot, 76100 Israel
Microcirculation 10:297-311. 2003..We propose that these two mechanisms are differentially used by distinct leukocyte subsets at various vascular beds, providing much larger combinatorial diversity of integrin activation on rolling leukocytes than previously predicted...
TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent mannerInbal Binsky
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
J Immunol 184:4761-9. 2010..These results could form the basis of novel therapeutic strategies aimed at blocking homing of CLL cells in their return to the BM and attenuating their survival...
A real time in vitro assay for studying leukocyte transendothelial migration under physiological flow conditionsGuy Cinamon
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
J Immunol Methods 273:53-62. 2003..In the present review, we describe this new flow-based migration assay and discuss future applications for investigating TEM processes of different types of leukocytes across distinct endothelial barriers...
Endothelial chemokines destabilize L-selectin-mediated lymphocyte rolling without inducing selectin sheddingValentin Grabovsky
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
J Biol Chem 277:20640-50. 2002..This negative feedback mechanism may underlie the jerky nature of rolling mediated by L-selectin in vivo...
L-selectin dimerization enhances tether formation to properly spaced ligandOren Dwir
Department of Immunology, Weizmann Institute of Science, Rehovot, 76100 Israel
J Biol Chem 277:21130-9. 2002..This is the first indication that shear stress augments effective selectin ligand density at local contact sites by promoting L-selectin encounter of immobilized ligand...
A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and plateletsRonit Pasvolsky
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
J Exp Med 204:1571-82. 2007..Chemokine-triggered VLA-4 adhesiveness in T lymphocytes was partially defective as well. These studies identify CalDAG-GEFI as a critical regulator of inside-out integrin activation in human T lymphocytes, neutrophils, and platelets...
LAD-III, a novel group of leukocyte integrin activation deficienciesRonen Alon
Department of Immunology, The Weizmann Institute of Science, 76100 Rehovot, Israel
Trends Immunol 24:561-6. 2003..Here, the mechanisms by which GPCRs might regulate leukocyte and platelet integrins are outlined with respect to this new family of LAD cases. We propose to term this the LAD-III family...
Suppression of experimental autoimmune myasthenia gravis by inhibiting the signaling between IFN-gamma inducible protein 10 (IP-10) and its receptor CXCR3Tali Feferman
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
J Neuroimmunol 209:87-95. 2009..Treatment by either of these reagents led to suppression of EAMG suggesting that inhibition of CXCR3/IP-10 signaling can be considered as a potential treatment modality for MG...
Tumor suppressor death-associated protein kinase attenuates inflammatory responses in the lungSigal Nakav
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Am J Respir Cell Mol Biol 46:313-22. 2012..The DAPk-mediated suppression of lung inflammation and airway injury may contribute to the tumor-suppressor functions of this kinase in epithelial carcinogenesis...
TGF-beta1 enhances SDF-1alpha-induced chemotaxis and homing of naive T cells by up-regulating CXCR4 expression and downstream cytoskeletal effector moleculesSusanne Franitza
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Eur J Immunol 32:193-202. 2002..We propose that the effect of TGF-beta1 on the chemotaxis of naive T cells may be important in the locomotion of naive T cells toward SDF-1alpha-rich niches...
Role of CXCR3 carboxyl terminus and third intracellular loop in receptor-mediated migration, adhesion and internalization in response to CXCL11Michal Dagan-Berger
Gene Therapy Institute, Hadassah University Hospital, PO Box 12000, Jerusalem, Israel
Blood 107:3821-31. 2006..Thus, distinct conformational changes induced by a given CXCR3 ligand trigger different downstream effectors of adhesion, motility, and CXCR3 desensitization...
Shear flow-dependent integration of apical and subendothelial chemokines in T-cell transmigration: implications for locomotion and the multistep paradigmTaylor H Schreiber
Harvard Skin Disease Research Center and the Department of Dermatology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Blood 109:1381-6. 2007....
Elastase release by transmigrating neutrophils deactivates endothelial-bound SDF-1alpha and attenuates subsequent T lymphocyte transendothelial migrationRavi M Rao
Department of Pathology, Center for Excellence in Vascular Biology, Brigham and Women s Hospital, Harvard Medical School, 77 Ave Louis Pasteur NRB 752P, Boston, MA 02115, USA
J Exp Med 200:713-24. 2004..In summary, transmigrating neutrophils secrete localized elastase that is protected from plasma inhibitors, and thereby modulate trafficking of other leukocyte subsets by altering the endothelial-associated chemotactic activities...
Measurement of selectin tether bond lifetimesTimothy A Springer
Biophys J 83:2318-20; author reply 2320-3. 2002
Sialylation of ICAM-2 on platelets impairs adhesion of leukocytes via LFA-1 and DC-SIGNKim S C Weber
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Harvard Medical School, Boston, Massachusetts, USA
Inflammation 28:177-88. 2004..These findings demonstrated that physiologic sialylation of platelet ICAM-2 renders it less able than endothelial ICAM-2 to support adherence of leukocytes...
Differential usage of VLA-4 and CXCR4 by CD3+CD56+ NKT cells and CD56+CD16+ NK cells regulates their interaction with endothelial cellsSuzanna Franitza
Hadassah University Hospital, Goldyne Savad Gene Therapy Institute, Jerusalem, Israel
Eur J Immunol 34:1333-41. 2004..This study therefore suggests an important role for CXCR4 levels of expression and for VLA-4 in regulating the accumulation of NKT cells in the BM...
Integrin modulation and signaling in leukocyte adhesion and migrationDavid M Rose
Department of Medicine, University of California, and VA Healthcare System, San Diego, CA, USA
Immunol Rev 218:126-34. 2007..We describe mechanisms through which alpha4beta1 integrin signaling regulates appropriate Rac activation to drive leukocyte migration...
Kindlin-3: a new gene involved in the pathogenesis of LAD-IIIAdi Mory
Blood 112:2591. 2008
Leukocyte adhesion deficiency III: a group of integrin activation defects in hematopoietic lineage cellsAmos Etzioni
Meyer Children s Hospital, B Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
Curr Opin Allergy Clin Immunol 4:485-90. 2004..The clinical manifestations and molecular basis of this syndrome and related cases will be reviewed...
ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alpha-activated vascular endothelium under flowLin Yang
Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB 752P, Boston, MA 02215, USA
Blood 106:584-92. 2005..In summary, ICAM-1 promotes junctional and nonjunctional TEM across inflamed vascular endothelium via distinct cytoplasmic tail associations...
Immature leukemic CD34+CXCR4+ cells from CML patients have lower integrin-dependent migration and adhesion in response to the chemokine SDF-1Amnon Peled
Hadassah University Hospital, Gene Therapy Institutem, Jerusalem, Israel
Stem Cells 20:259-66. 2002..These findings suggest a major role for SDF-1-mediated, integrin-dependent BM retention of Ph+CD34+ cells...
Immune cell migration in inflammation: present and future therapeutic targetsAndrew D Luster
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
Nat Immunol 6:1182-90. 2005....
Synthetic glycoprotein mimics inhibit L-selectin-mediated rolling and promote L-selectin sheddingPatricia Mowery
Department of Biochemistry, 433 Babcock Drive, University of Wisconsin-Madison, Madison, WI 53706 USA
Chem Biol 11:725-32. 2004..Thus, their inhibitory potency may arise from their ability to induce shedding. Our data indicate that screening for compounds that promote L-selectin release can identify ligands that inhibit rolling...
Rolling on N-linked glycans: a new way to present L-selectin binding sitesRonen Alon
Nat Immunol 8:339-41. 2007
L-selectin-mediated leukocyte tethering in shear flow is controlled by multiple contacts and cytoskeletal anchorage facilitating fast rebinding eventsUlrich S Schwarz
Theory Division, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
Proc Natl Acad Sci U S A 101:6940-5. 2004....
Crawling and INTEGRating apical cuesRonen Alon
Nat Immunol 5:351-3. 2004
LAD III versus LAD I variantAmos Etzioni
Blood 110:4129; author reply 4129-30. 2007
