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Leishmania lipophosphoglycan reduces monocyte transendothelial migration: modulation of cell adhesion molecules, intercellular junctional proteins, and chemoattractants. 1998

S K Lo, and L Bovis, and R Matura, and B Zhu, and S He, and H Lum, and S J Turco, and J L Ho
Department of Medicine, Cornell University Medical College, NY 10021, USA. sklo@mail.med.cornell.edu

We previously identified the structural requirement for the inhibitory activity of Leishmania lipophosphoglycan (LPG) to block endothelial adhesion to monocytes. Here we showed that LPG reduces transendothelial migration of monocytes. LPG pretreatment of endothelial cells (2 microM, 1 h) reduced monocyte migration across endothelial cells activated by bacterial endotoxin (LPS) or IL-1beta (60 and 46%, respectively). A fragment of LPG (i.e., repeating phosphodisaccharide (consisting of galactosyl-mannose)) and LPG coincubated with LPG-neutralizing mAb lacks inhibitory activity on monocyte migration. Pretreatment of monocytes with LPG (2 microM, 1 h) also did not affect monocyte migration through control or LPS-activated endothelial cells. FACS analysis reveals that LPG treatment blocked the LPS-mediated expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 on endothelial cells and monocyte adhesion without altering the integrity of the endothelial monolayer. LPG (2 microM, 1 h) alone was capable of altering the expression and distribution of two junctional adhesion molecules, CD31 and vascular endothelium cadherin, as well as reversing the effects of LPS on these proteins. The induction of endothelial cells by LPS to transcribe and release monocyte chemoattractant protein-1 (MCP-1) was significantly reduced by LPG (40-65%). LPG treatment of nonactivated endothelial cells also suppressed by 55 to 75% the monocyte migration triggered by a MCP-1 chemoattractant gradient, and coincubation of LPG with neutralizing mAb abrogated the inhibitory activity. Together, these data point to a novel anti-inflammatory function of LPG in reducing monocyte migration across endothelial cells via a mechanism of inhibition of endothelial expression of cell adhesion molecules, modulation of intercellular junctional proteins, and synthesis of MCP-1.

UI MeSH Term Description Entries
D007365 Intercellular Junctions Direct contact of a cell with a neighboring cell. Most such junctions are too small to be resolved by light microscopy, but they can be visualized by conventional or freeze-fracture electron microscopy, both of which show that the interacting CELL MEMBRANE and often the underlying CYTOPLASM and the intervening EXTRACELLULAR SPACE are highly specialized in these regions. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p792) Cell Junctions,Cell Junction,Intercellular Junction,Junction, Cell,Junction, Intercellular,Junctions, Cell,Junctions, Intercellular
D007893 Leishmania donovani A parasitic hemoflagellate of the subgenus Leishmania leishmania that infects man and animals and causes visceral leishmaniasis (LEISHMANIASIS, VISCERAL). The sandfly genera Phlebotomus and Lutzomyia are the vectors. Leishmania (Leishmania) donovani,Leishmania leishmania donovani,Leishmania donovanus,Leishmania leishmania donovanus,donovani, Leishmania leishmania,donovanus, Leishmania,donovanus, Leishmania leishmania,leishmania donovanus, Leishmania
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D002464 Cell Migration Inhibition Phenomenon of cell-mediated immunity measured by in vitro inhibition of the migration or phagocytosis of antigen-stimulated LEUKOCYTES or MACROPHAGES. Specific CELL MIGRATION ASSAYS have been developed to estimate levels of migration inhibitory factors, immune reactivity against tumor-associated antigens, and immunosuppressive effects of infectious microorganisms. Chemotaxis Inhibition,Chemotaxis Inhibitions,Inhibition, Chemotaxis,Inhibitions, Chemotaxis
D002630 Chemotactic Factors Chemical substances that attract or repel cells. The concept denotes especially those factors released as a result of tissue injury, microbial invasion, or immunologic activity, that attract LEUKOCYTES; MACROPHAGES; or other cells to the site of infection or insult. Chemoattractant,Chemotactic Factor,Chemotaxin,Chemotaxins,Cytotaxinogens,Cytotaxins,Macrophage Chemotactic Factor,Chemoattractants,Chemotactic Factors, Macrophage,Macrophage Chemotactic Factors,Chemotactic Factor, Macrophage,Factor, Chemotactic,Factor, Macrophage Chemotactic
D002634 Chemotaxis, Leukocyte The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction. Leukotaxis,Leukocyte Chemotaxis
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006028 Glycosphingolipids Lipids containing at least one monosaccharide residue and either a sphingoid or a ceramide (CERAMIDES). They are subdivided into NEUTRAL GLYCOSPHINGOLIPIDS comprising monoglycosyl- and oligoglycosylsphingoids and monoglycosyl- and oligoglycosylceramides; and ACIDIC GLYCOSPHINGOLIPIDS which comprises sialosylglycosylsphingolipids (GANGLIOSIDES); SULFOGLYCOSPHINGOLIPIDS (formerly known as sulfatides), glycuronoglycosphingolipids, and phospho- and phosphonoglycosphingolipids. (From IUPAC's webpage) Asialoganglioside,Asialogangliosides,Glycosphingolipid,Sphingoglycolipid,Sphingoglycolipids
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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