A5023164058- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune responses and vaccinations
- Proteoglycans and glycosaminoglycans research
- Inflammasome and immune disorders
- interferon and immune responses
- Fatty Acid Research and Health
- Immunotherapy and Immune Responses
- Signaling Pathways in Disease
- Sepsis Diagnosis and Treatment
- Extracellular vesicles in disease
- Eicosanoids and Hypertension Pharmacology
- Inflammatory Bowel Disease
- Infant Nutrition and Health
- Monoclonal and Polyclonal Antibodies Research
- Peroxisome Proliferator-Activated Receptors
- Platelet Disorders and Treatments
- Macrophage Migration Inhibitory Factor
- Cytokine Signaling Pathways and Interactions
- Galectins and Cancer Biology
- Cancer Cells and Metastasis
University of Haifa
2016-2025
Brigham and Women's Hospital
2003-2007
Harvard University
2003-2006
Boston University
2006
Massachusetts General Hospital
2006
Weizmann Institute of Science
1997-2002
Sheba Medical Center
2001
Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density (LDNs) that appear transiently self-resolving inflammation but accumulate continuously with progression. LDNs display impaired immunosuppressive properties, characteristics are stark contrast those mature, high-density (HDNs). consist immature myeloid-derived suppressor cells (MDSCs) mature derived from HDNs...
Abstract The cellular events underlying the resolution of acute inflammation are not known in molecular terms. To identify anti-inflammatory and proresolving circuits, we investigated temporal differential changes self-resolving murine exudates using mass spectrometry-based proteomics lipidomics. Key components were defined as indices including Ψmax, maximal neutrophil numbers that present during inflammatory response; Tmax, time when Ψmax occurs; interval (Ri) from Tmax to T50 reach half...
Despite the remarkable success of anti-cancer immunotherapy, its effectiveness remains confined to a subset patients—emphasizing importance predictive biomarkers in clinical decision-making and further mechanistic understanding treatment response. Current biomarkers, however, lack power required accurately stratify patients. Here, we identify interferon-stimulated, Ly6Ehi neutrophils as blood-borne biomarker anti-PD1 response mice at baseline. are induced by tumor-intrinsic activation STING...
Docosahexaenoic acid, a major omega-3 fatty acid in human brain, synapses, retina, and other neural tissues, displays beneficial actions neuronal development, cancer, inflammatory diseases by mechanisms that remain to be elucidated. In this study we found, using lipid mediator informatics employing liquid chromatography-tandem mass spectrometry, (10,17S)-docosatriene/neuroprotectin D1, now termed protectin D1 (PD1), is generated from docosahexaenoic T helper type 2-skewed peripheral blood...
During the resolution phase of inflammation, apoptotic leukocytes are efferocytosed by macrophages in a nonphlogistic fashion that results diminished responses to bacterial moieties and production anti-inflammatory cytokines. Complement receptor 3 pro-resolving lipid mediators promote engulfment macrophages. Here, we present evidence for emergence pro-resolving, CD11b(low) vivo during murine peritonitis. These distinct from majority peritoneal terms their functional protein expression...
Elevated extracellular K+ ([K+]o), in the absence of “classical” immunological stimulatory signals, was found to itself be a sufficient stimulus activate T cell β1 integrin moieties, and induce integrin-mediated adhesion migration. Gating voltage-gated channels (Kv1.3) appears crucial “decision-making” step, through which various physiological factors, including elevated [K+]o levels, affect function: opening channel leads function, whereas its blockage prevents it. In support this notion,...
Monocytes that migrate into tissues during inflammatory episodes and differentiate to macrophages were previously classified as classically (M1) or alternatively (M2) activated macrophages, based on their exposure different fate-determining mediators. These macrophage subsets display distinct molecular markers differential functions. At the same time, studies from recent years found encounter of apoptotic leukocytes with leads clearance this cellular "debris" by while concomitantly...
Abstract The uptake of apoptotic polymorphonuclear cells (PMN) by macrophages is critical for timely resolution inflammation. High-burden associated with loss phagocytosis in phase macrophages. Here, using a transcriptomic analysis macrophage subsets, we show that non-phagocytic express distinct IFN-β-related gene signature mice. We also report elevated levels IFN-β peritoneal and broncho-alveolar exudates mice during the peritonitis pneumonia, respectively. Elimination endogenous impairs,...
Neutrophils provide first line of host defense against bacterial infections utilizing glycolysis for their effector functions. How and its major byproduct lactate are triggered in bone marrow (BM) neutrophils contribution to neutrophil mobilization acute inflammation is not clear. Here we report that lipopolysaccharides (LPS) or Salmonella Typhimurium triggers release by increasing glycolysis, NADPH-oxidase-mediated reactive oxygen species HIF-1α levels BM neutrophils. Increased...
Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that associated granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined PR3 on surface apoptotic neutrophils interferes induction antiinflammatory mechanisms following phagocytosis these cells by macrophages. Here, we demonstrate enzymatically active membrane-associated triggered secretion inflammatory cytokines,...
Abstract Lipoxins (LX) and their aspirin-triggered 15-epimer endogenous isoforms are anti-inflammatory pro-resolution eicosanoids. In this study, we examined the impact of LX LXA4-stable analogs (ATLa) on human T cell functions. 15-epi-16-(p-fluoro)phenoxy-LXA4 (ATLa1) blocked secretion TNF-α from PBMC after stimulation by anti-CD3 Abs, with IC50 value ≈0.05 nM. A similar action was also exerted native 15-epi-LXA4, a new 15-epi-16-(p-trifluoro)phenoxy-LXA4 analog (ATLa2), as well LXB4, its...
Neutrophils are polymorphonuclear leukocytes that play a central role in host defense against infection and tissue injury. They rapidly recruited to the inflamed site execute variety of functions clear invading pathogens damaged cells. However, many their mechanisms capable inflicting collateral damage. Neutrophil-driven inflammation is unifying mechanism underlying common diseases. Efficient removal neutrophils from inflammatory loci critical for timely resolution return homeostasis....
The complete resolution of inflammation requires the uptake apoptotic polymorphonuclear cells (PMN) by local macrophages (efferocytosis) and consequent reprogramming engulfing phagocytes to reparative pro-resolving phenotypes. tyrosine kinase receptors TYRO3, AXL, MERTK (collectively named TAM) are fundamental mediators in regulating inflammatory responses efferocytosis. Protein S (PROS1) is a ligand for all TAM that mediates various aspects their activity. However, involvement PROS1...
During the resolution of acute inflammation, macrophages undergo reprogramming from pro-inflammatory, to anti-inflammatory/reparative, and eventually pro-resolving macrophages. Galectin-1 (Gal-1) is a bona fide lectin while interferon β (IFN-β) was recently shown facilitate macrophage inflammation. In this study, we found Gal-1null mice exhibit hyperinflammatory phenotype during zymosan A-induced peritonitis but not early inflammatory response. This characterized by reduced numbers,...
EDITORIAL article Front. Immunol., 01 November 2012Sec. Inflammation Volume 3 - 2012 | https://doi.org/10.3389/fimmu.2012.00324