Leishmania Lipophosphoglycan Reduces Monocyte Transendothelial Migration: Modulation of Cell Adhesion Molecules, Intercellular Junctional Proteins, and Chemoattractants
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 mon...
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| Veröffentlicht in: | The Journal of immunology (1950) 1998-02, Vol.160 (4), p.1857-1865 |
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| container_title | The Journal of immunology (1950) |
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| creator | Lo, Siu K Bovis, Lisa Matura, Rosemarie Zhu, Baixin He, Suhui Lum, Hazel Turco, Salvatore J Ho, John L |
| description | 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. |
| doi_str_mv | 10.4049/jimmunol.160.4.1857 |
| format | Article |
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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.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.160.4.1857</identifier><identifier>PMID: 9469447</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Animals ; Antigens, CD ; Cadherins - biosynthesis ; Cadherins - metabolism ; Cell Adhesion - drug effects ; Cell Adhesion - immunology ; Cell Adhesion Molecules - biosynthesis ; Cell Adhesion Molecules - metabolism ; Cell Migration Inhibition ; Chemokine CCL2 - antagonists & inhibitors ; Chemokine CCL2 - biosynthesis ; Chemokine CCL2 - pharmacology ; Chemotactic Factors - metabolism ; Chemotaxis, Leukocyte - drug effects ; Chemotaxis, Leukocyte - immunology ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - immunology ; Glycosphingolipids - pharmacology ; Humans ; Intercellular Junctions - immunology ; Intercellular Junctions - metabolism ; Leishmania donovani - immunology ; Monocytes - immunology ; Monocytes - physiology ; Platelet Endothelial Cell Adhesion Molecule-1 - biosynthesis ; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</subject><ispartof>The Journal of immunology (1950), 1998-02, Vol.160 (4), p.1857-1865</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c363t-6843a26540c8ede137efa9ac65714a118524fbc7c97ff9989151f2a6118290103</citedby><cites>FETCH-LOGICAL-c363t-6843a26540c8ede137efa9ac65714a118524fbc7c97ff9989151f2a6118290103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9469447$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lo, Siu K</creatorcontrib><creatorcontrib>Bovis, Lisa</creatorcontrib><creatorcontrib>Matura, Rosemarie</creatorcontrib><creatorcontrib>Zhu, Baixin</creatorcontrib><creatorcontrib>He, Suhui</creatorcontrib><creatorcontrib>Lum, Hazel</creatorcontrib><creatorcontrib>Turco, Salvatore J</creatorcontrib><creatorcontrib>Ho, John L</creatorcontrib><title>Leishmania Lipophosphoglycan Reduces Monocyte Transendothelial Migration: Modulation of Cell Adhesion Molecules, Intercellular Junctional Proteins, and Chemoattractants</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>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.</description><subject>Animals</subject><subject>Antigens, CD</subject><subject>Cadherins - biosynthesis</subject><subject>Cadherins - metabolism</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Adhesion - immunology</subject><subject>Cell Adhesion Molecules - biosynthesis</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell Migration Inhibition</subject><subject>Chemokine CCL2 - antagonists & inhibitors</subject><subject>Chemokine CCL2 - biosynthesis</subject><subject>Chemokine CCL2 - pharmacology</subject><subject>Chemotactic Factors - metabolism</subject><subject>Chemotaxis, Leukocyte - drug effects</subject><subject>Chemotaxis, Leukocyte - immunology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - immunology</subject><subject>Glycosphingolipids - pharmacology</subject><subject>Humans</subject><subject>Intercellular Junctions - immunology</subject><subject>Intercellular Junctions - metabolism</subject><subject>Leishmania donovani - immunology</subject><subject>Monocytes - immunology</subject><subject>Monocytes - physiology</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - biosynthesis</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd-OEyEYxYnRrN3VJzAmXLk3OxVmGCjebRr_rGmjMes1YZlvOmwYqMCk6Rv5mDK2Gu-8IJDv_M6BcBB6RcmSESbfPtpxnHxwS8rLZElXrXiCFrRtScU54U_RgpC6rqjg4jm6TOmREMJJzS7QhWRcMiYW6OcGbBpG7a3GG7sP-yGksnbuaLTH36CbDCS8DT6YYwZ8H7VP4LuQB3BWO7y1u6izDf5dgbrJ_T7j0OM1OIdvuwHSPNgGB2ZykG7wnc8QTVELHPHnyZvZUqK-xpDB-oJo3-H1AGPQOUdtsvY5vUDPeu0SvDzvV-j7h_f360_V5svHu_XtpjINb3LFV6zRNW8ZMSvogDYCei214a2gTNPyRzXrH4wwUvS9lCtJW9rXmhelloSS5gq9OeXuY_gxQcpqtGl-rvYQpqSELFdwIv4LUt4wyWpZwOYEmhhSitCrfbSjjkdFiZqLVH-KLJ4yUXORxfX6HD89jND99ZybK_r1SR_sbjjYCCqN2rlCU3U4HP5J-gUA_q1d</recordid><startdate>19980215</startdate><enddate>19980215</enddate><creator>Lo, Siu K</creator><creator>Bovis, Lisa</creator><creator>Matura, Rosemarie</creator><creator>Zhu, Baixin</creator><creator>He, Suhui</creator><creator>Lum, Hazel</creator><creator>Turco, Salvatore J</creator><creator>Ho, John L</creator><general>Am Assoc Immnol</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>19980215</creationdate><title>Leishmania Lipophosphoglycan Reduces Monocyte Transendothelial Migration: Modulation of Cell Adhesion Molecules, Intercellular Junctional Proteins, and Chemoattractants</title><author>Lo, Siu K ; Bovis, Lisa ; Matura, Rosemarie ; Zhu, Baixin ; He, Suhui ; Lum, Hazel ; Turco, Salvatore J ; Ho, John L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c363t-6843a26540c8ede137efa9ac65714a118524fbc7c97ff9989151f2a6118290103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Antigens, CD</topic><topic>Cadherins - biosynthesis</topic><topic>Cadherins - metabolism</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Adhesion - immunology</topic><topic>Cell Adhesion Molecules - biosynthesis</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cell Migration Inhibition</topic><topic>Chemokine CCL2 - antagonists & inhibitors</topic><topic>Chemokine CCL2 - biosynthesis</topic><topic>Chemokine CCL2 - pharmacology</topic><topic>Chemotactic Factors - metabolism</topic><topic>Chemotaxis, Leukocyte - drug effects</topic><topic>Chemotaxis, Leukocyte - immunology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - immunology</topic><topic>Glycosphingolipids - pharmacology</topic><topic>Humans</topic><topic>Intercellular Junctions - immunology</topic><topic>Intercellular Junctions - metabolism</topic><topic>Leishmania donovani - immunology</topic><topic>Monocytes - immunology</topic><topic>Monocytes - physiology</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - biosynthesis</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lo, Siu K</creatorcontrib><creatorcontrib>Bovis, Lisa</creatorcontrib><creatorcontrib>Matura, Rosemarie</creatorcontrib><creatorcontrib>Zhu, Baixin</creatorcontrib><creatorcontrib>He, Suhui</creatorcontrib><creatorcontrib>Lum, Hazel</creatorcontrib><creatorcontrib>Turco, Salvatore J</creatorcontrib><creatorcontrib>Ho, John L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lo, Siu K</au><au>Bovis, Lisa</au><au>Matura, Rosemarie</au><au>Zhu, Baixin</au><au>He, Suhui</au><au>Lum, Hazel</au><au>Turco, Salvatore J</au><au>Ho, John L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leishmania Lipophosphoglycan Reduces Monocyte Transendothelial Migration: Modulation of Cell Adhesion Molecules, Intercellular Junctional Proteins, and Chemoattractants</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>1998-02-15</date><risdate>1998</risdate><volume>160</volume><issue>4</issue><spage>1857</spage><epage>1865</epage><pages>1857-1865</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>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.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>9469447</pmid><doi>10.4049/jimmunol.160.4.1857</doi><tpages>9</tpages></addata></record> |
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| ispartof | The Journal of immunology (1950), 1998-02, Vol.160 (4), p.1857-1865 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Antigens, CD Cadherins - biosynthesis Cadherins - metabolism Cell Adhesion - drug effects Cell Adhesion - immunology Cell Adhesion Molecules - biosynthesis Cell Adhesion Molecules - metabolism Cell Migration Inhibition Chemokine CCL2 - antagonists & inhibitors Chemokine CCL2 - biosynthesis Chemokine CCL2 - pharmacology Chemotactic Factors - metabolism Chemotaxis, Leukocyte - drug effects Chemotaxis, Leukocyte - immunology Endothelium, Vascular - drug effects Endothelium, Vascular - immunology Glycosphingolipids - pharmacology Humans Intercellular Junctions - immunology Intercellular Junctions - metabolism Leishmania donovani - immunology Monocytes - immunology Monocytes - physiology Platelet Endothelial Cell Adhesion Molecule-1 - biosynthesis Platelet Endothelial Cell Adhesion Molecule-1 - metabolism |
| title | Leishmania Lipophosphoglycan Reduces Monocyte Transendothelial Migration: Modulation of Cell Adhesion Molecules, Intercellular Junctional Proteins, and Chemoattractants |
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