Abstract:
:Immune and inflammatory cells play a critical role in the pathogenesis of atherosclerotic plaques. We have demonstrated that A2ARs inhibit foam cell formation and stimulate production of ABCA1, the primary transporter of lipoproteins. We asked whether the effects of A2ARs on foam cell formation in vitro are mediated by transporters involved in reverse cholesterol transport, ABCA1 and ABCG1. Foam cells were generated from THP-1 cells by incubation with 100 nM PMA for 2 days and incubated with acLDL (50 microg/mL) plus IFN-gamma (500 U/mL) +/- A2AR agonist CGS-21680 (1 microM). Radiolabeled cholesterol (0.2 microCi/ml) was added to cells, and efflux was measured using a liquid scintillation counter. Lentiviral siRNA infection markedly reduces ABCA1 or ABCG1 mRNA in THP-1 cells. Despite diminished ABCG1 expression (KD), CGS-21680 inhibits foam cell formation (81+5% inhibition; P<0.0001 vs. IFN-gamma alone; n=3) but has no effect on foam cell formation in ABCA1 KD cells (5+3% inhibition; P<0.85 vs. IFN-gamma alone; n=3). The A2A agonist increases apoA-I-mediated cholesterol efflux nearly twofold in THP-1-derived macrophages (from 9.5% to 17.5+2.5% [3H]-cholesterol efflux; P<0.0090 vs. control; n=3) but not in ABCA1 KD cells. Activation of Epac, a signaling molecule downstream of the A2AR, increased ABCA1 (23+5%; P<0.0007 vs. control; n=3) and phospho-ABCA1 (13+5%; P<0.0003 vs. control; n=3) protein. These results demonstrate that A2AR occupancy diminishes foam cell formation by stimulating increased reverse cholesterol transport via ABCA1.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Bingham TC,Fisher EA,Parathath S,Reiss AB,Chan ES,Cronstein BNdoi
10.1189/jlb.0709513subject
Has Abstractpub_date
2010-04-01 00:00:00pages
683-90issue
4eissn
0741-5400issn
1938-3673pii
jlb.0709513journal_volume
87pub_type
杂志文章abstract::We have shown that losartan, a selective inhibitor of AT1 receptors for angiotensin II (AII), inhibits the binding of [3H]fMLP to neutrophil receptors (FPR). Here, we analyze, in Wistar rats, the effect of losartan on neutrophil recruitment in the lung triggered by fMLP. We found that i.v. infusion of losartan (0.4-20...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::There is accumulating evidence that omega-3 fatty acids may modulate immune responses. When monocytes were differentiated to dendritic cells (DCs) in the presence of docosahexaenoic acid (DHA), the expression of costimulatory and antigen presentation markers was altered in a concentration-dependent way, positively or ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1007688
更新日期:2008-10-01 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::Human CD4+CD25+ regulatory T (T(R)) cells express the transcription factor forkhead box p3 (FOXP3) and have potent immunosuppressive properties. While naturally occurring T(R) cells develop in the thymus, adaptive T(R) cells develop in the periphery from naive CD4+ T cells. Adaptive T(R) cells may express cyclooxygena...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0507329
更新日期:2008-05-01 00:00:00
abstract::Apoptosis of polymorphonuclear leukocytes (PMNs) is a critical step in the resolution of tissue inflammation. PMN apoptosis has been studied extensively in vitro, and diverse inflammatory mediators have been shown to modulate the process. The reported effects of interleukin-6 (IL-6) on PMN apoptosis are inconsistent; ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.58.5.582
更新日期:1995-11-01 00:00:00
abstract::Osteoarticular complications are common in human brucellosis, but the pathogenic mechanisms involved are largely unknown. In this manuscript, we described an immune mechanism for inflammatory bone loss in response to infection by Brucella abortus. We established a requirement for MyD88 and TLR2 in TNF-α-elicited osteo...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.04111185
更新日期:2012-02-01 00:00:00
abstract::The interaction between CD40 on dendritic cells (DC) and its ligand CD154 has been recognized to be an important feature in the maturation of DC. Here, we were interested in the role of CD44 a surface receptor shown to mediate cell-cell adhesion and binding to Hyaluronic acid (HA). Western blot analysis of human DC st...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract::Impairments in the respiratory burst and stimulus-response coupling were studied with respect to the increased rate of cell replication that occurred in HL60 cells during repetitive passages in cell culture. During a 45-week period of culture, HL60 cells developed a progressive increase in rate of replication. Concomi...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.52.2.157
更新日期:1992-08-01 00:00:00
abstract::Constitutive expression of cell-associated, but not secreted, interleukin-1alpha (IL-1alpha) by oncogene-transformed fibrosarcoma cells induced regressing tumors in mice, a phenomenon that was abrogated by the IL-1 inhibitor, the IL-1 receptor antagonist (IL-1Ra). On the contrary, non-IL-1alpha-expressing tumor cells ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0905509
更新日期:2006-07-01 00:00:00
abstract::To determine if the release of IL-1 alpha and IL-1 beta by cultured PBMC could be independently modulated by different exogenous stimuli, we examined the effect of LPS, IFN gamma, latex beads, and indomethacin on the release of IL-1 alpha and IL-1 beta. PBMC culture supernatants were fractionated by Sephacryl-S-200 co...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.46.5.417
更新日期:1989-11-01 00:00:00
abstract::Nitric oxide (NO) is a well-documented effector molecule in rodent phagocytes but its synthesis in human neutrophils has been controversial. In this study, NO production in human neutrophils activated by chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) was measured in the presence of L-arginine (L-Ar...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.66.1.127
更新日期:1999-07-01 00:00:00
abstract::Granulocyte-colony stimulating factor (G-CSF) is an essential cytokine, which contributes to proliferation and differentiation of granulocyte precursor cells in the bone marrow. Despite recent progress in understanding G-CSF signaling events, the mechanisms that underlie the distinct spectrum of biological functions a...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0205066
更新日期:2006-05-01 00:00:00
abstract::Dendritic cells (DC) are professional antigen-presenting cells that are used in vaccine approaches to cancer. Classically, mature monocyte-derived DC are generated in vitro in the presence of interleukin (IL)-4, granulocyte macrophage-colony stimulating factor, and inflammatory cytokines (G4-DC). Recently, it has been...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0105052
更新日期:2005-10-01 00:00:00
abstract::Underlying acquired immunity to the fungus Candida albicans is usually present in adult immunocompetent individuals and is presumed to prevent mucosal colonization progressing to symptomatic infection. Exploration of immunological events leading to Candida resistance or susceptibility has indicated the central role of...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:
更新日期:2000-08-01 00:00:00
abstract::IL-1β is an important mediator of innate inflammatory responses and has been shown to contribute to liver injury in a number of etiologies. HIV patients have increased necroinflammation and more rapid fibrosis progression in chronic liver injury compared to non-HIV-infected patients. As the resident liver macrophage i...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.4A1018-381R
更新日期:2019-04-01 00:00:00
abstract::The restriction of herpes simplex virus type 1 (HSV-1) gene expression in nonpermissive murine resident peritoneal macrophages (ResPMO) was analyzed at the level of transcription. Using nuclear run-on assays, we established that transcription of a representative gene from each HSV-1 kinetic class was initiated in both...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.53.1.61
更新日期:1993-01-01 00:00:00
abstract::Prostaglandins function as down regulators of immune responses probably by increasing the concentration of intracellular cAMP. Phosphodiesterase inhibitors, which prevent the breakdown of cAMP, also increase the intracellular levels of cAMP. Prostaglandins and phosphodiesterase inhibitors have both been shown to suppr...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.47.4.371
更新日期:1990-04-01 00:00:00
abstract::CD163, a monocyte and macrophage-specific surface glycoprotein, which is increased by interleukin-10 and glucocorticoids, is a scavenger receptor for hemoglobin/haptoglobin complexes. We report a rapid and highly reproducible rise in soluble CD163 in the plasma of human volunteers given intravenous lipopolysaccharide ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract::THP-1 cells are a monocyte-like cell line derived from a patient with acute monocytic leukemia and unlike other leukemic cell lines has a normal diploid karyotype. We have characterized Fc gamma R expression on this cell line by flow cytometry, radiolabeled IgG1 and monoclonal antibody (mAb) binding assays, and bioche...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.49.6.556
更新日期:1991-06-01 00:00:00
abstract::A protein with interleukin 1 (IL-1) activity was obtained from the human acute monocytic leukemia cell line (THP-1) and purified by ultrafiltration, Ultrogel AcA54 chromatography, isoelectric focusing, and discontinuous polyacrylamide gel electrophoresis. Like the pI 6.8 species of IL-1 from human peripheral blood mon...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.37.5.511
更新日期:1985-05-01 00:00:00
abstract::Antagonism of ROS signaling can inhibit cell apoptosis and autophagy, thus favoring the maintenance and expansion of hematopoietic stem cells. Alpha lipoic acid (ALA), a small antioxidant molecule, affects cell apoptosis by lowering the ROS level. In this study, we show that ALA promoted production of human pluripoten...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.1A0520-179R
更新日期:2020-12-01 00:00:00
abstract::Eosinophils are generally linked to innate host defense against helminths, as well as the pathologies associated with allergic diseases, such as asthma. Nonetheless, the activities of eosinophils remain poorly understood, which in turn, has prevented detailed definitions of their role(s) in health and disease. Homolog...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0213089
更新日期:2013-07-01 00:00:00
abstract::Although endosomes, lysosomes, and phagosomes require a reductive environment for the optimal activity of disulfide reductases and other thiol-dependent enzymes, how these reductive environments are established and maintained remain unknown. Our goal in this study was to begin to elucidate the redox control systems re...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.2HI0315-083R
更新日期:2016-07-01 00:00:00
abstract::Neutrophils are indispensable in the innate immune defense against invading microorganisms. Neutrophils contain SVs and several subsets of granules that are essential for their function. Proteins present in neutrophil SVs and granules are synthesized during terminal granulopoiesis in the bone marrow. The heterogeneity...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1212619
更新日期:2013-10-01 00:00:00
abstract::Vertebrate lectin purified from loach egg was tested for induction of tumor lysis mediated by macrophages. Loach egg lectin lysed tumor cells but not normal spleen cells in cooperation with BCG- or glucan (TAK)-elicited peritoneal macrophages of mice. Corynebacterium parvum-, OK432-, glycogen-, lipopolysaccharide-elic...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.35.3.241
更新日期:1984-03-01 00:00:00
abstract::Leucocyte-endothelial cell interactions are important in the inflammatory response. In this study, the effect of peripheral blood mononuclear cell (PBMC) products on endothelial cell (EC) shape was examined and quantified. PBMC were obtained from normal donors by Ficoll-Hypaque separation of heparinized whole blood an...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.41.5.421
更新日期:1987-05-01 00:00:00
abstract::Role of IL-18 on proliferation and survival of CD8+ T cells, activated by immobilized anti-CD3 antibody (anti-CD3), was examined. Proliferation and survival of activated T cells, especially that of CD8+ T cells, were impaired by IL-18 deficiency [IL-18 knockout (KO)]. After 3 days of culture with anti-CD3, the number ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0706431
更新日期:2007-07-01 00:00:00
abstract::The human cathelicidin LL-37 is a cationic host defense peptide (antimicrobial peptide) expressed primarily by neutrophils and epithelial cells. This peptide, up-regulated under conditions of inflammation, has immunomodulatory and antimicrobial functions. We demonstrate that LL-37 is a potent inhibitor of human neutro...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1005560
更新日期:2006-09-01 00:00:00
abstract::During inflammatory and immunological responses, leukocytes respond to external stimuli by altering the stability of cytokine and cytokine receptor messages. Change in message stability is an effective mechanism for rapidly regulating steady state levels of mRNA. Cytokine messages containing A-U-rich elements located ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.62.5.653
更新日期:1997-11-01 00:00:00
abstract::Tumor necrosis factor (TNF)-stimulated gene 14 (TSG-14, also termed PTX3) encodes a secreted glycoprotein whose carboxy-terminal half shares sequence similarity with the pentraxin family of acute phase proteins (C-reactive protein and serum amyloid P component). We compared TSG-14 mRNA expression in cultures of murine...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.67.3.387
更新日期:2000-03-01 00:00:00