Tryptophanyl tRNA Synthetase from Human Macrophages Infected by Porphyromonas gingivalis Induces a Proinflammatory Response Associated with Atherosclerosis

Porphyromonas gingivalis is the most common microorganism associated with adult periodontal disease, causing inflammation around the subgingival lesion. In this study, we investigated tryptophanyl tRNA synthase (WRS) production by THP-1 cells infected with P. gingivalis. Cytokine production, leukocyte adhesion molecules, and low-density lipoprotein receptor (LDLR) expressions in cultured cells were examined. WRS was detected in THP-1 cell culture supernatants stimulated with P. gingivalis from 1 to 24 h, and apparent production was observed after 4 h. No change in WRS mRNA expression was observed from 1 to 6 h in THP-1 cells, whereas its expression was significantly increased 12 h after stimulation with P. gingivalis. Lactate dehydrogenase (LDH) activity was observed from 4 to 24 h. The TNF-α, IL-6, IL-8, and CXCL2 levels of THP-1 cells were upregulated after treatment with recombinant WRS (rWRS) and were significantly reduced when THP-1 cells were treated with C29. The MCP-1, ICAM-1, and VCAM-1 levels in human umbilical vein endothelial cells were upregulated following treatment with rWRS, and TAK242 suppressed these effects. Additionally, unmodified LDLR, macrophage scavenger receptor A, and lectin-like oxidized LDLRs were upregulated in THP-1 cells treated with rWRS. These results suggest that WRS from macrophages infected with P. gingivalis is associated with atherosclerosis.

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Modification of Delipidated Apoprotein B of Low Density Lipoprotein by Lipid Oxidation Products in Relation to Macrophage Scavenger Receptor Binding.

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.17.51 ◽

1994 ◽

Vol 17 (1) ◽

pp. 51-57 ◽

Cited By ~ 22

Author(s):

Manuel ALAIZ ◽

Masatoshi BEPPU ◽

Kenji OHISHI ◽

Kiyomi KIKUGAWA

Keyword(s):

Lipid Oxidation ◽

Receptor Binding ◽

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

Oxidation Products ◽

Low Density ◽

Macrophage Scavenger Receptor ◽

Lipid Oxidation Products ◽

Apoprotein B

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LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells

Biochemical Journal ◽

10.1042/bj20051166 ◽

2005 ◽

Vol 393 (1) ◽

pp. 107-115 ◽

Cited By ~ 57

Author(s):

Jane E. Murphy ◽

Daryl Tacon ◽

Philip R. Tedbury ◽

Jonathan M. Hadden ◽

Stuart Knowling ◽

...

Keyword(s):

Cultured Cells ◽

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

Low Density ◽

Dependent Manner ◽

Oxidized Low Density Lipoprotein ◽

Bivalent Cation ◽

Calcium Dependent

The LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) scavenger receptor regulates vascular responses to oxidized-low-density-lipoprotein particles implicated in atherosclerotic plaque formation. LOX-1 is closely related to C-type lectins, but the mechanism of ligand recognition is not known. Here we show that human LOX-1 recognizes a key cellular phospholipid, PS (phosphatidylserine), in a Ca2+-dependent manner, both in vitro and in cultured cells. A recombinant, folded and glycosylated LOX-1 molecule binds PS, but not other phospholipids. LOX-1 recognition of PS was maximal in the presence of millimolar Ca2+ levels. Mg2+ was unable to substitute for Ca2+ in LOX-1 binding to PS, indicating a Ca2+-specific requirement for bivalent cations. LOX-1-mediated recognition of PS-containing apoptotic bodies was dependent on Ca2+ and was decreased to background levels by bivalent-cation chelation, LOX-1-blocking antibodies or PS-containing liposomes. The LOX-1 membrane protein is thus a Ca2+-dependent phospholipid receptor, revealing novel recognition of phospholipids by mammalian lectins.

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CD36 in atherosclerosis

Nepalese Heart Journal ◽

10.3126/njh.v9i1.8349 ◽

2013 ◽

Vol 9 (1) ◽

pp. 47-50

Author(s):

Dhruba Acharya

Keyword(s):

Retinal Pigment ◽

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

Cell Types ◽

Type I ◽

Microvascular Endothelium ◽

Major Band ◽

Anionic Phospholipids ◽

Macrophage Scavenger Receptor

CD36 was described nearly 30 years ago as “glycoprotein IV” the fourth major band of 88KD observed on SDS-PAGE of platelet membrane (1). It is present on many mammalian cell types: microvascular endothelium; professional phagocytes including macrophages, dendritic cells, microglia and retinal pigment-epithellium; erythroid precursors; hepatocytes; adipocytes; cardiac and skeletal myocytes; and specialized epithelia of the breast, kidney and gut (2). As a pattern recognition receptor, CD36 binds a diverse set of ligands, including oxidized low-density lipoprotein (oxLDL)(5), anionic phospholipids (4), long-chain fatty acids, thrombospondin-1, fibrillar -amyloid, and the membrane of cells undergoing apoptosis (3, 5, 6). CD36 has been implicated in a wide variety of normal and pathologic biological functions, including angiogenesis, atherosclerosis, phagocytosis, inflammation, lipid metabolism, and removal of apoptotic cells (3, 5). In 1993, Endemann et al. first identified CD36 as a potential oxLDL receptor (7).Unlike macrophage scavenger receptor A type I and II, CD36 binds LDL that has been exposed to minimally oxidizing condition. The observation that CD36 was an oxLDL receptor was the catalyst for many to prove the role of CD36 in atherosclerosis. DOI: http://dx.doi.org/10.3126/njh.v9i1.8349 Nepalese Heart Journal Vol.9(1) 2012 pp.47-50

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M-CSF-induced macropinocytosis increases solute endocytosis but not receptor-mediated endocytosis in mouse macrophages

Journal of Cell Science ◽

10.1242/jcs.102.4.867 ◽

1992 ◽

Vol 102 (4) ◽

pp. 867-880 ◽

Cited By ~ 10

Author(s):

E.L. Racoosin ◽

J.A. Swanson

Keyword(s):

Lucifer Yellow ◽

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

Coated Vesicles ◽

Human Macrophage ◽

Murine Bone Marrow ◽

Receptor Mediated Endocytosis ◽

Macrophage Scavenger Receptor ◽

Diferric Transferrin

Although coated vesicles can mediate both solute and receptor-mediated endocytosis, there are other kinds of endocytic vesicles that contribute to these processes. The relative contributions of these other organelles, particularly regarding solute influx, remains unsettled. Here we describe a physiological uncoupling of solute and receptor-mediated endocytosis that occurs during growth factor-stimulated macropinocytosis. We examined how recombinant human macrophage colony-stimulating factor (rM-CSF), which rapidly stimulates solute endocytosis in murine bone marrow-derived macrophages, affected ligand internalization via receptor-mediated endocytosis. Although rM-CSF stimulated internalization and accumulation of Lucifer Yellow (LY), a probe for solute endocytosis, it had no effect on accumulation of fluorescent acetylated low-density lipoprotein (acLDL), a ligand for the macrophage scavenger receptor, or on the endocytosis of 125I-labelled diferric transferrin. Video microscopy revealed that rM-CSF immediately induced active cell ruffling and the formation of phase-bright macropinosomes. Nocodazole pretreatment of macrophages inhibited both ruffling and macropinocytosis. Macropinosomes were fluorescently labelled by incubating macrophages briefly with probes for both solute endocytosis (fluorescent dextrans) and ligand endocytosis (fluorescein-labelled transferrin or diI-labelled acLDL). Macrophages incubated for one or two minutes formed macropinosomes that were labelled predominantly with the fluorescent solute probes but with little or none of the ligand probes; the latter were localized within smaller pinosomes. When cells pulsed with the fluorescent probes were washed and chased for an additional two minutes, solute and ligand probes occasionally co-localized in macropinosomes. Nocodazole inhibited macropinocytosis with little apparent effect on endocytosis via smaller vesicles. These experiments show that macropinosome formation is dependent on microtubules and also that the macropinosomes induced by rM-CSF are solute-rich and receptor-poor. Macropinosomes differ from coated vesicles in these respects, and therefore provide a physiologically regulated mechanism for uncoupling solute and receptor-mediated endocytosis.

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