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ATP-Gated P2X7 Receptors Require Chloride Channels To Promote Inflammation in Human Macrophages
Immune cells of myeloid origin show robust expression of ATP-gated P2X7 receptors, two-transmembrane ion channels permeable to Na , K , and Ca Receptor activation promotes inflammasome activation and release of the proinflammatory cytokines IL-1β and IL-18. In this study, we show that ATP generates...
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| Published in: | The Journal of immunology (1950) 2019-02, Vol.202 (3), p.883-898 |
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| Main Authors: | , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c396t-1a0a43086be3b0015791ca6bf661909c257e962f497d70de1ca32f8fd42e332c3 |
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| cites | cdi_FETCH-LOGICAL-c396t-1a0a43086be3b0015791ca6bf661909c257e962f497d70de1ca32f8fd42e332c3 |
| container_end_page | 898 |
| container_issue | 3 |
| container_start_page | 883 |
| container_title | The Journal of immunology (1950) |
| container_volume | 202 |
| creator | Janks, Laura Sprague, Randy S Egan, Terrance M |
| description | Immune cells of myeloid origin show robust expression of ATP-gated P2X7 receptors, two-transmembrane ion channels permeable to Na
, K
, and Ca
Receptor activation promotes inflammasome activation and release of the proinflammatory cytokines IL-1β and IL-18. In this study, we show that ATP generates facilitating cationic currents in monocyte-derived human macrophages and permeabilizes the plasma membrane to polyatomic cationic dyes. We find that antagonists of PLA
and Cl
channels abolish P2X7 receptor-mediated current facilitation, membrane permeabilization, blebbing, phospholipid scrambling, inflammasome activation, and IL-1β release. Our data demonstrate significant differences in the actions of ATP in murine and human macrophages and suggest that PLA
and Cl
channels mediate innate immunity downstream of P2X7 receptors in human macrophages. |
| doi_str_mv | 10.4049/jimmunol.1801101 |
| format | article |
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, K
, and Ca
Receptor activation promotes inflammasome activation and release of the proinflammatory cytokines IL-1β and IL-18. In this study, we show that ATP generates facilitating cationic currents in monocyte-derived human macrophages and permeabilizes the plasma membrane to polyatomic cationic dyes. We find that antagonists of PLA
and Cl
channels abolish P2X7 receptor-mediated current facilitation, membrane permeabilization, blebbing, phospholipid scrambling, inflammasome activation, and IL-1β release. Our data demonstrate significant differences in the actions of ATP in murine and human macrophages and suggest that PLA
and Cl
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, K
, and Ca
Receptor activation promotes inflammasome activation and release of the proinflammatory cytokines IL-1β and IL-18. In this study, we show that ATP generates facilitating cationic currents in monocyte-derived human macrophages and permeabilizes the plasma membrane to polyatomic cationic dyes. We find that antagonists of PLA
and Cl
channels abolish P2X7 receptor-mediated current facilitation, membrane permeabilization, blebbing, phospholipid scrambling, inflammasome activation, and IL-1β release. Our data demonstrate significant differences in the actions of ATP in murine and human macrophages and suggest that PLA
and Cl
channels mediate innate immunity downstream of P2X7 receptors in human macrophages.</description><subject>Adenosine Triphosphate - metabolism</subject><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Cells, Cultured</subject><subject>Chloride Channels - antagonists & inhibitors</subject><subject>Chloride Channels - immunology</subject><subject>Cytokines - immunology</subject><subject>Female</subject><subject>Humans</subject><subject>Immunity, Innate</subject><subject>Inflammation</subject><subject>Macrophages - immunology</subject><subject>Male</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Phospholipase A2 Inhibitors</subject><subject>Phospholipases A2 - immunology</subject><subject>Receptors, Purinergic P2X1 - genetics</subject><subject>Receptors, Purinergic P2X4 - genetics</subject><subject>Receptors, Purinergic P2X7 - immunology</subject><subject>Signal Transduction</subject><subject>Young Adult</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpVUU1LAzEUDKJo_bh7khy9rL4ku9nmIkjRWlAsUsFbSHff2sgmqcmu4L93i1X09AbezLyPIeSUwUUOubp8s871PrQXbAyMAdshI1YUkEkJcpeMADjPWCnLA3KY0hsASOD5PjkQUKhxwcoR0deLeTY1HdZ0zl9K-oQVrrsQ04DeexuRTlZtiLbeAOM9tokuAp3H4EKHdOab1jhnOhs8tZ7e9c54-mCqGNYr84rpmOw1pk14sq1H5Pn2ZjG5y-4fp7PJ9X1WCSW7jBkwuYCxXKJYArCiVKwyctlIyRSoihclKsmbXJV1CTUOTcGbcVPnHIXglTgiV9--637psK7Qd9G0eh2tM_FTB2P1_463K_0aPrQUBVcMBoPzrUEM7z2mTjubKmxb4zH0SXMm-TB9-PNAhW_qcGVKEZvfMQz0Jhf9k4ve5jJIzv6u9yv4CUJ8Acaoi58</recordid><startdate>20190201</startdate><enddate>20190201</enddate><creator>Janks, Laura</creator><creator>Sprague, Randy S</creator><creator>Egan, Terrance M</creator><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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4589-600X</orcidid></search><sort><creationdate>20190201</creationdate><title>ATP-Gated P2X7 Receptors Require Chloride Channels To Promote Inflammation in Human Macrophages</title><author>Janks, Laura ; Sprague, Randy S ; Egan, Terrance M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-1a0a43086be3b0015791ca6bf661909c257e962f497d70de1ca32f8fd42e332c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adenosine Triphosphate - metabolism</topic><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Cells, Cultured</topic><topic>Chloride Channels - antagonists & inhibitors</topic><topic>Chloride Channels - immunology</topic><topic>Cytokines - immunology</topic><topic>Female</topic><topic>Humans</topic><topic>Immunity, Innate</topic><topic>Inflammation</topic><topic>Macrophages - immunology</topic><topic>Male</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Phospholipase A2 Inhibitors</topic><topic>Phospholipases A2 - immunology</topic><topic>Receptors, Purinergic P2X1 - genetics</topic><topic>Receptors, Purinergic P2X4 - genetics</topic><topic>Receptors, Purinergic P2X7 - immunology</topic><topic>Signal Transduction</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Janks, Laura</creatorcontrib><creatorcontrib>Sprague, Randy S</creatorcontrib><creatorcontrib>Egan, Terrance M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Janks, Laura</au><au>Sprague, Randy S</au><au>Egan, Terrance M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ATP-Gated P2X7 Receptors Require Chloride Channels To Promote Inflammation in Human Macrophages</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2019-02-01</date><risdate>2019</risdate><volume>202</volume><issue>3</issue><spage>883</spage><epage>898</epage><pages>883-898</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Immune cells of myeloid origin show robust expression of ATP-gated P2X7 receptors, two-transmembrane ion channels permeable to Na
, K
, and Ca
Receptor activation promotes inflammasome activation and release of the proinflammatory cytokines IL-1β and IL-18. In this study, we show that ATP generates facilitating cationic currents in monocyte-derived human macrophages and permeabilizes the plasma membrane to polyatomic cationic dyes. We find that antagonists of PLA
and Cl
channels abolish P2X7 receptor-mediated current facilitation, membrane permeabilization, blebbing, phospholipid scrambling, inflammasome activation, and IL-1β release. Our data demonstrate significant differences in the actions of ATP in murine and human macrophages and suggest that PLA
and Cl
channels mediate innate immunity downstream of P2X7 receptors in human macrophages.</abstract><cop>United States</cop><pmid>30598517</pmid><doi>10.4049/jimmunol.1801101</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-4589-600X</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of immunology (1950), 2019-02, Vol.202 (3), p.883-898 |
| issn | 0022-1767 1550-6606 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6352910 |
| source | EZB Electronic Journals Library |
| subjects | Adenosine Triphosphate - metabolism Adult Aged Animals Cell Line Cells, Cultured Chloride Channels - antagonists & inhibitors Chloride Channels - immunology Cytokines - immunology Female Humans Immunity, Innate Inflammation Macrophages - immunology Male Mice Middle Aged Phospholipase A2 Inhibitors Phospholipases A2 - immunology Receptors, Purinergic P2X1 - genetics Receptors, Purinergic P2X4 - genetics Receptors, Purinergic P2X7 - immunology Signal Transduction Young Adult |
| title | ATP-Gated P2X7 Receptors Require Chloride Channels To Promote Inflammation in Human Macrophages |
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