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Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis
Leukocyte transmigration across vessel walls is a critical step in the innate immune response. Upon their activation and firm adhesion to vascular endothelial cells (VECs), leukocytes preferentially extravasate across junctional gaps in the endothelial monolayer (paracellular diapedesis). It has bee...
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Published in: | Proceedings of the National Academy of Sciences - PNAS 2018-01, Vol.115 (1), p.133-138 |
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description | Leukocyte transmigration across vessel walls is a critical step in the innate immune response. Upon their activation and firm adhesion to vascular endothelial cells (VECs), leukocytes preferentially extravasate across junctional gaps in the endothelial monolayer (paracellular diapedesis). It has been hypothesized that VECs facilitate paracellular diapedesis by opening their cell–cell junctions in response to the presence of an adhering leukocyte. However, it is unclear how leukocytes interact mechanically with VECs to open the VEC junctions and migrate across the endothelium. In this study, we measured the spatial and temporal evolution of the 3D traction stresses generated by the leukocytes and VECs to elucidate the sequence of mechanical events involved in paracellular diapedesis. Our measurements suggest that the contractile stresses exerted by the leukocytes and the VECs can separately perturb the junctional tensions of VECs to result in the opening of gaps before the initiation of leukocyte transmigration. Decoupling the stresses exerted by the transmigrating leukocytes and the VECs reveals that the leukocytes actively contract the VECs to open a junctional gap and then push themselves across the gap by generating strong stresses that push into the matrix. In addition, we found that diapedesis is facilitated when the tension fluctuations in the VEC monolayer were increased by proinflammatory thrombin treatment. Our findings demonstrate that diapedesis can be mechanically regulated by the transmigrating leukocytes and by proinflammatory signals that increase VEC contractility. |
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Upon their activation and firm adhesion to vascular endothelial cells (VECs), leukocytes preferentially extravasate across junctional gaps in the endothelial monolayer (paracellular diapedesis). It has been hypothesized that VECs facilitate paracellular diapedesis by opening their cell–cell junctions in response to the presence of an adhering leukocyte. However, it is unclear how leukocytes interact mechanically with VECs to open the VEC junctions and migrate across the endothelium. In this study, we measured the spatial and temporal evolution of the 3D traction stresses generated by the leukocytes and VECs to elucidate the sequence of mechanical events involved in paracellular diapedesis. Our measurements suggest that the contractile stresses exerted by the leukocytes and the VECs can separately perturb the junctional tensions of VECs to result in the opening of gaps before the initiation of leukocyte transmigration. Decoupling the stresses exerted by the transmigrating leukocytes and the VECs reveals that the leukocytes actively contract the VECs to open a junctional gap and then push themselves across the gap by generating strong stresses that push into the matrix. In addition, we found that diapedesis is facilitated when the tension fluctuations in the VEC monolayer were increased by proinflammatory thrombin treatment. Our findings demonstrate that diapedesis can be mechanically regulated by the transmigrating leukocytes and by proinflammatory signals that increase VEC contractility.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1717489115</identifier><identifier>PMID: 29255056</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Biological Sciences ; Cell activation ; Cell adhesion & migration ; Cell junctions ; Cells ; Contractility ; Decoupling ; Diapedesis ; Endothelial cells ; Endothelium ; Extravasation ; HL-60 Cells ; Human Umbilical Vein Endothelial Cells - cytology ; Human Umbilical Vein Endothelial Cells - metabolism ; Humans ; Immune response ; Immune system ; Inflammation ; Innate immunity ; Intercellular Junctions - metabolism ; Leukocyte migration ; Leukocytes ; Leukocytes - cytology ; Leukocytes - metabolism ; Medical treatment ; Models, Biological ; Monolayers ; Stresses ; Thrombin ; Transendothelial and Transepithelial Migration - physiology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2018-01, Vol.115 (1), p.133-138</ispartof><rights>Volumes 1–89 and 106–114, copyright as a collective work only; author(s) retains copyright to individual articles</rights><rights>Copyright National Academy of Sciences Jan 2, 2018</rights><rights>2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-21282f0c7c7520a72b7be5c8bac0b278eb6ed9f0751d80bcf25e7ab311935b53</citedby><cites>FETCH-LOGICAL-c509t-21282f0c7c7520a72b7be5c8bac0b278eb6ed9f0751d80bcf25e7ab311935b53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26506289$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26506289$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792,58237,58470</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29255056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yeh, Yi-Ting</creatorcontrib><creatorcontrib>Serrano, Ricardo</creatorcontrib><creatorcontrib>François, Joshua</creatorcontrib><creatorcontrib>Chiu, Jeng-Jiann</creatorcontrib><creatorcontrib>Li, Yi-Shuan Julie</creatorcontrib><creatorcontrib>del Álamo, Juan C.</creatorcontrib><creatorcontrib>Chien, Shu</creatorcontrib><creatorcontrib>Lasheras, Juan C.</creatorcontrib><title>Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Leukocyte transmigration across vessel walls is a critical step in the innate immune response. Upon their activation and firm adhesion to vascular endothelial cells (VECs), leukocytes preferentially extravasate across junctional gaps in the endothelial monolayer (paracellular diapedesis). It has been hypothesized that VECs facilitate paracellular diapedesis by opening their cell–cell junctions in response to the presence of an adhering leukocyte. However, it is unclear how leukocytes interact mechanically with VECs to open the VEC junctions and migrate across the endothelium. In this study, we measured the spatial and temporal evolution of the 3D traction stresses generated by the leukocytes and VECs to elucidate the sequence of mechanical events involved in paracellular diapedesis. Our measurements suggest that the contractile stresses exerted by the leukocytes and the VECs can separately perturb the junctional tensions of VECs to result in the opening of gaps before the initiation of leukocyte transmigration. Decoupling the stresses exerted by the transmigrating leukocytes and the VECs reveals that the leukocytes actively contract the VECs to open a junctional gap and then push themselves across the gap by generating strong stresses that push into the matrix. In addition, we found that diapedesis is facilitated when the tension fluctuations in the VEC monolayer were increased by proinflammatory thrombin treatment. Our findings demonstrate that diapedesis can be mechanically regulated by the transmigrating leukocytes and by proinflammatory signals that increase VEC contractility.</description><subject>Biological Sciences</subject><subject>Cell activation</subject><subject>Cell adhesion & migration</subject><subject>Cell junctions</subject><subject>Cells</subject><subject>Contractility</subject><subject>Decoupling</subject><subject>Diapedesis</subject><subject>Endothelial cells</subject><subject>Endothelium</subject><subject>Extravasation</subject><subject>HL-60 Cells</subject><subject>Human Umbilical Vein Endothelial Cells - cytology</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Inflammation</subject><subject>Innate immunity</subject><subject>Intercellular Junctions - metabolism</subject><subject>Leukocyte migration</subject><subject>Leukocytes</subject><subject>Leukocytes - cytology</subject><subject>Leukocytes - metabolism</subject><subject>Medical treatment</subject><subject>Models, Biological</subject><subject>Monolayers</subject><subject>Stresses</subject><subject>Thrombin</subject><subject>Transendothelial and Transepithelial Migration - physiology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpdkc1v1DAQxS0EokvhzAkUiUsvacdOHNsXJFRRQKrEZe-WPyasF2-82EnV_Pck2tICp5FmfvM0bx4hbylcUhDN1XEw5ZIKKlqpKOXPyIaConXXKnhONgBM1LJl7Rl5VcoeABSX8JKcMcU4B95tSNruMmLtwwGHEtJgYtWn7LBUeI95RF_ZuYo4_UxuHpeuGXx1Z4qboskVDj6NO4xh2XIYY6n8PJhDcCbGueqNCzGMZsTKB3NEjyWU1-RFb2LBNw_1nGxvPm-vv9a33798u_50WzsOaqwZZZL14IQTnIERzAqL3ElrHFgmJNoOvepBcOolWNczjsLYhlLVcMubc_LxJHuc7AG9w2HMJupjDgeTZ51M0P9OhrDTP9Kd5kJ0knWLwMWDQE6_JiyjPoSyejQDpqloqoQUrFViRT_8h-7TlJdPrpSiXDaMqYW6OlEup1Iy9o_HUNBrlnrNUj9luWy8_9vDI_8nvAV4dwL2ZUz5ad5x6JhUzW9vLafe</recordid><startdate>20180102</startdate><enddate>20180102</enddate><creator>Yeh, Yi-Ting</creator><creator>Serrano, Ricardo</creator><creator>François, Joshua</creator><creator>Chiu, Jeng-Jiann</creator><creator>Li, Yi-Shuan Julie</creator><creator>del Álamo, Juan C.</creator><creator>Chien, Shu</creator><creator>Lasheras, Juan C.</creator><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180102</creationdate><title>Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis</title><author>Yeh, Yi-Ting ; 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Upon their activation and firm adhesion to vascular endothelial cells (VECs), leukocytes preferentially extravasate across junctional gaps in the endothelial monolayer (paracellular diapedesis). It has been hypothesized that VECs facilitate paracellular diapedesis by opening their cell–cell junctions in response to the presence of an adhering leukocyte. However, it is unclear how leukocytes interact mechanically with VECs to open the VEC junctions and migrate across the endothelium. In this study, we measured the spatial and temporal evolution of the 3D traction stresses generated by the leukocytes and VECs to elucidate the sequence of mechanical events involved in paracellular diapedesis. Our measurements suggest that the contractile stresses exerted by the leukocytes and the VECs can separately perturb the junctional tensions of VECs to result in the opening of gaps before the initiation of leukocyte transmigration. Decoupling the stresses exerted by the transmigrating leukocytes and the VECs reveals that the leukocytes actively contract the VECs to open a junctional gap and then push themselves across the gap by generating strong stresses that push into the matrix. In addition, we found that diapedesis is facilitated when the tension fluctuations in the VEC monolayer were increased by proinflammatory thrombin treatment. Our findings demonstrate that diapedesis can be mechanically regulated by the transmigrating leukocytes and by proinflammatory signals that increase VEC contractility.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>29255056</pmid><doi>10.1073/pnas.1717489115</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Biological Sciences Cell activation Cell adhesion & migration Cell junctions Cells Contractility Decoupling Diapedesis Endothelial cells Endothelium Extravasation HL-60 Cells Human Umbilical Vein Endothelial Cells - cytology Human Umbilical Vein Endothelial Cells - metabolism Humans Immune response Immune system Inflammation Innate immunity Intercellular Junctions - metabolism Leukocyte migration Leukocytes Leukocytes - cytology Leukocytes - metabolism Medical treatment Models, Biological Monolayers Stresses Thrombin Transendothelial and Transepithelial Migration - physiology |
title | Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis |
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