Abstract：
:In inflammatory diseases, circulating neutrophils are recruited to sites of injury. Attractant signals are provided by many different chemotactic molecules, such that blockade of one may not prevent neutrophil recruitment effectively. The Slit family of secreted proteins and their transmembrane receptor, Robo, repel axonal migration during CNS development. Emerging evidence shows that by inhibiting the activation of Rho-family GTPases, Slit2/Robo also inhibit migration of other cell types toward a variety of chemotactic factors in vitro and in vivo. The role of Slit2 in inflammation, however, has been largely unexplored. We isolated primary neutrophils from human peripheral blood and mouse bone marrow and detected Robo-1 expression. Using video-microscopic live cell tracking, we found that Slit2 selectively impaired directional migration but not random movement of neutrophils toward fMLP. Slit2 also inhibited neutrophil migration toward other chemoattractants, namely C5a and IL-8. Slit2 inhibited neutrophil chemotaxis by preventing chemoattractant-induced actin barbed end formation and cell polarization. Slit2 mediated these effects by suppressing inducible activation of Cdc42 and Rac2 but did not impair activation of other major kinase pathways involved in neutrophil migration. We further tested the effects of Slit2 in vivo using mouse models of peritoneal inflammation induced by sodium periodate, C5a, and MIP-2. In all instances, Slit2 reduced neutrophil recruitment effectively (P<0.01). Collectively, these data demonstrate that Slit2 potently inhibits chemotaxis but not random motion of circulating neutrophils and point to Slit2 as a potential new therapeutic for preventing localized inflammation.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Tole S,Mukovozov IM,Huang YW,Magalhaes MA,Yan M,Crow MR,Liu GY,Sun CX,Durocher Y,Glogauer M,Robinson LAdoi
10.1189/jlb.0609391subject
Has Abstractpub_date
2009-12-01 00:00:00pages
1403-15issue
6eissn
0741-5400issn
1938-3673pii
jlb.0609391journal_volume
86pub_type
杂志文章abstract：:cDNA cloning revealed the presence of two related but distinct types of human interleukin-8 (IL-8) receptors, type I (type A) and type II (type B). By immunizing rabbits with glutathione-S-transferase fused with the NH2-terminal domain of each type of IL-8 receptor, we prepared polyclonal antibodies that specifically ...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.57.1.180
更新日期：1995-01-01 00:00:00
abstract：:Macrophages play major roles in the onset of immune responses and inflammation by inducing a variety of cytokines such as TNF and IFN-beta. The pathogen-associated molecular pattern, polyinosinic-polycytidylic acid [poly(I:C)], and LPS were used to study type-I IFN and TNF responses in human macrophages. Additionally,...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.0607412
更新日期：2008-05-01 00:00:00
abstract：:Feline peritoneal cells were collected by lavage with isotonic saline without the use of irritants or need for euthanasia of the cats. Macrophages were purified by centrifugation on Percoll followed by selective adherence. Although few macrophages could be obtained from an initial lavage, a second lavage performed on ...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.44.5.319
更新日期：1988-11-01 00:00:00
abstract：:An in vitro system allowing the culture of ovine bone marrow-derived macrophages (BMMs) is described. Bone marrow (BM) cells from the sternum of 4- to 9-month-old sheep were cultured in liquid suspension in hydrophobic bags with medium containing 20% autologous serum and 20% fetal calf serum (FCS). Cells with macropha...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.51.6.525
更新日期：1992-06-01 00:00:00
abstract：:The germinal center (GC) is a dynamic structure formed by proliferating B cells in the follicles of secondary lymphoid organs during T cell-dependent antibody responses to exogenous antigens. GC is composed by a dark zone, enriched in proliferating centroblasts (CBs), and a light zone where CBs migrate and transform i...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章,评审
doi：10.1189/jlb.1VMR0216-096RR
更新日期：2016-11-01 00:00:00
abstract：:In this study we describe the isolation and characterization of a new chicken (Gallus gallus) chemokine. This molecule belongs to the C or gamma-chemokine family and is related to the mouse and human lymphotactin (Lptn). Mouse and human Lptn are distinguished from alpha and beta chemokines by the absence of two cystei...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.65.1.87
更新日期：1999-01-01 00:00:00
abstract：:The effect of platelets and their products on in vitro responses of human neutrophils to f-met-leu-phe (fMLP) and phorbol myristate acetate (PMA) was studied. Platelets produced a concentration-dependent inhibition of neutrophil superoxide anion (O2-) generation with maximum inhibition of the response to fMLP approach...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.44.2.93
更新日期：1988-08-01 00:00:00
abstract：:Effector T cell development is directly driven by APCs, in particular, by antigen-primed dendritic cells (DCs). Depending on the pathogenic stimulus and the microenvironment, DCs induce proliferation and polarization of naive CD4+ T cells into different effector subsets, such as Th1, Th2, Th17, or regulatory T cells (...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章,评审
doi：10.1189/jlb.4MR0217-048RR
更新日期：2017-10-01 00:00:00
abstract：:In the presence of adenosine, formyl-Met-Leu-Phe-stimulated human neutrophils show a greatly diminished production of superoxide anion. Analysis of changes in levels of intracellular calcium revealed that the immediate increase (occurring within seconds) in intracellular calcium following addition of formyl-Met-Leu-Ph...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.48.3.281
更新日期：1990-09-01 00:00:00
abstract：:Intact cellular migration is critically important for the induction and regulation of the immune response. The Wiskott-Aldrich syndrome protein (WASP) regulates surface receptor signaling to the actin cytoskeleton in hematopoietic cells and thus plays a pivotal role in cellular locomotion. WASP deficiency causes the W...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.0804444
更新日期：2005-06-01 00:00:00
abstract：:Tissue macrophages produce several proteins of the complement system. The mechanisms that regulate this process are poorly understood. The established ability of certain prostaglandins to influence macrophage secretory activity suggests that these lipid mediators may also modulate complement production (CP). Using the...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.37.5.651
更新日期：1985-05-01 00:00:00
abstract：:The mechanisms by which concanavalin A (Con A), a lectin, activates T cells are poorly studied. A low dose of Con A is stimulatory for T cells, whereas a high dose of Con A results in suppression of proliferation and enhanced T cell death. The expression and functional roles of costimulatory receptors, CD28 and cytoto...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.1104644
更新日期：2005-07-01 00:00:00
abstract：:The relationship between leukocyte migration and parenchymal cell death in vivo remains poorly documented. Accordingly, cell killing in the rat mesentery, as recorded by propidium iodide staining, was investigated with an intravital approach. Superfusion of platelet-activating factor (PAF, 10(-8) M) or N-formyl-methio...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.62.2.163
更新日期：1997-08-01 00:00:00
abstract：:HL-60 cells are promyelocytic leukemia cells that respond to culture conditions with differentiation into granulocytelike or macrophagelike phagocytes. O2 metabolism is critical to the microbicidal function of phagocytic cells. O2 metabolism was studied in HL-60 cells differentiated with dimethylsulfoxide (Me2SO) and ...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.43.2.140
更新日期：1988-02-01 00:00:00
abstract：:HIV infection causes rapid and lasting defects in the population of Vgamma2Vdelta2 T cells. To fully describe the impact of HIV, we examined PBMC samples from HIV+ patients receiving highly active antiretroviral therapy, who had displayed prolonged viral control and CD4 counts above 300 cells/mm3. We observed lower fr...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.1207847
更新日期：2008-08-01 00:00:00
abstract：:Type I IFNs are used for treating viral, neoplastic, and inflammatory disorders. The protein products encoded by IFN-stimulated genes (ISGs) likely mediate clinical effects of IFN in patients. Macroarray assays, used for studying ISG induction in IFN-treated patients, comprise genes identified predominantly through an...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.0507273
更新日期：2007-11-01 00:00:00
abstract：:This short review focuses on the role of central nervous system (CNS) perivascular macrophages as targets of productive infection of the CNS. Data discussed include the importance of these cells as early targets of infection and their productive infection with AIDS. Many of the immune molecules on perivascular macroph...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章,评审
doi：10.1189/jlb.0503207
更新日期：2003-11-01 00:00:00
abstract：:An anti-macrophage monoclonal antibody designated TRPM-3 was produced using thioglycollate-elicited rat peritoneal macrophages as immunogen. By the immunoperoxidase method, TRPM-3 was found to be specific for certain macrophage populations, such as marginal zone macrophages and marginal metallophils of the spleen, sin...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.41.3.187
更新日期：1987-03-01 00:00:00
abstract：:The role of JNK in neutrophil chemotaxis and killing of microbial pathogens remains unclear. Using a recently described cell-permeable peptide inhibitor of the JNK pathway, based on the JBD of JIP-1, coupled to the protein transduction domain of HIV-TAT (TAT-JIP), in association with control peptides, we demonstrate t...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.0609399
更新日期：2010-05-01 00:00:00
abstract：:M-CSF is a pleiotropic cytokine involved in the survival, proliferation, and differentiation of cells of the monocyte/macrophage lineage. M-CSF is produced by numerous cells including CD3-activated T cells. M-CSF serum levels are increased during acute graft rejection. We tested the in vitro production of M-CSF, GM-CS...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：
更新日期：2002-02-01 00:00:00
abstract：:The macrophage mannose receptor (MR) appears to play an important role in the binding and phagocytosis of several human pathogens, but its phagocytic property and signaling pathways have been poorly defined. The general strategy to explore such topics is to express the protein of interest in nonphagocytic cells, but i...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.1204705
更新日期：2005-06-01 00:00:00
abstract：:The motheaten mouse was first described in 1975 as a model of systemic inflammation and autoimmunity, as a result of immune system dysregulation. The phenotype was later ascribed to mutations in the cytoplasmic tyrosine phosphatase Shp1. This phosphatase is expressed widely throughout the hematopoietic system and has ...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章,评审
doi：10.1189/jlb.2MR0317-105R
更新日期：2017-09-01 00:00:00
abstract：:Inflammation-limiting nonsteroidal pain relievers magnify myocardial infarction (MI) incidences and increase re-admission events in heart failure (HF) patients. However, the molecular and cellular mechanism of this provocative adverse effect is unclear. Our goal was to determine whether carprofen (CAP) impedes splenic...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/JLB.3A0618-223R
更新日期：2018-12-01 00:00:00
abstract：:Blood leukocyte count alterations induced by PAF-acether in anesthetized and nonanesthetized rats were investigated. Intravenous injection of increasing amounts of PAF-acether (1.5-8 micrograms/kg) in nonanesthetized animals induced dose-dependent hemoconcentration and leukocytosis. The former was apparent within 10 m...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.51.2.146
更新日期：1992-02-01 00:00:00
abstract：:Complex syndromes such as atherosclerosis and type 2 diabetes are disorders that are associated with inflammatory processes involving innate and adaptive immunity. Emerging knowledge about the pathological consequences of immune imbalances in a wide range of disease settings is expected to help to identify novel thera...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.1003454
更新日期：2004-04-01 00:00:00
abstract：:IL-31, a newly identified member of the IL-6 cytokine family, is involved in many pathological conditions, including atopic dermatitis and pruritis. In this study, we investigated how expression of IL-31 is regulated in T cells and mast cells. We observed that expression of IL-31 required a calcium signal and was depe...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.0111020
更新日期：2012-02-01 00:00:00
abstract：:The synthesis and secretion of prostaglandins and leukotrienes by mouse peritoneal macrophages is under several regulatory controls. Arachidonic acid must first be released from phospholipid stores by the action of phospholipases. Macrophages have the capacity to deacylate arachidonic acid directly from the SN2 positi...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1002/jlb.35.1.1
更新日期：1984-01-01 00:00:00
abstract：:IL-10 is a key anti-inflammatory cytokine secreted by activated macrophages as a feedback control mechanism to prevent excessive inflammatory responses. Here, we define multiple intracellular trafficking pathways involved in the secretion of newly synthesized IL-10 from macrophages following TLR4 activation with LPS, ...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.0412191
更新日期：2012-12-01 00:00:00
abstract：:Endotoxin tolerance is characterized by attenuated macrophage activation to subsequent LPS challenge and can be reversed through nonspecific protein kinase C (PKC) activation, and activation by LPS within naïve cells requires the activation of the cell surface receptors CD14 and TLR4 on lipid rafts. The effect of PKC ...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.0106053
更新日期：2006-12-01 00:00:00
abstract：:Antigen presentation to T lymphocytes has been characterized extensively in terms of T lymphocyte activation and eventual cell death. In contrast, little is known about the consequences of antigen presentation for the antigen-presenting cell (APC). We have determined the outcome of major histocompatibility complex cla...
journal_title：Journal of leukocyte biology
pub_type： 杂志文章
doi：10.1189/jlb.0703356
更新日期：2004-06-01 00:00:00
