Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice
Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. W...
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| Veröffentlicht in: | The Journal of experimental medicine 1995-02, Vol.181 (2), p.569-575 |
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| container_title | The Journal of experimental medicine |
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| creator | Abraham, E Bursten, S Shenkar, R Allbee, J Tuder, R Woodson, P Guidot, D M Rice, G Singer, J W Repine, J E |
| description | Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss. |
| doi_str_mv | 10.1084/jem.181.2.569 |
| format | Article |
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We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. 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We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss.</description><subject>Acyltransferases - antagonists & inhibitors</subject><subject>Animals</subject><subject>Cell Adhesion</subject><subject>Cells, Cultured</subject><subject>Chemotaxis, Leukocyte</subject><subject>Cytokines - metabolism</subject><subject>Hemorrhage - metabolism</subject><subject>Humans</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Lung - metabolism</subject><subject>Lung - pathology</subject><subject>Mice</subject><subject>Pentoxifylline - analogs & derivatives</subject><subject>Pentoxifylline - pharmacology</subject><subject>Phosphatidic Acids - metabolism</subject><subject>Signal Transduction</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQRi0EKtuWI0eknLhlsR0nti9IqCpQqVJ7oGdrYo83XpJ4sRPE_nuMdlXBidNoZp4-zegR8pbRLaNKfNjjtGWKbfm27fQLsmGtoLVuG_WSbCjlvGaUytfkMuc9pUyItrsgF1I1nWZ8Q_LjEPNhgCW4YCuwwVU57GYYw7yrJnQBFszVuJbOHpf4PcxY4a9DwpxDnCuY3WkZZj_CNMES07E0-7UU8AumasAppjTADsu8moLFa_LKw5jxzblekafPt99uvtb3D1_ubj7d11ZIvdROMKe1aMDSXisvnFe9a3rqvBAKUDdNJ0E4RVlrpbfY-V7xHjjKjgNS0VyRj6fcw9qXVyzOS4LRHFKYIB1NhGD-3cxhMLv403CmmZJdCXh_Dkjxx4p5MVPIFscRZoxrNlKypmVc_xdkneRaCVXA-gTaFHNO6J-vYdT80WmKTlN0Gm6KzsK_-_uFZ_rsr_kNDJ-gLA</recordid><startdate>19950201</startdate><enddate>19950201</enddate><creator>Abraham, E</creator><creator>Bursten, S</creator><creator>Shenkar, R</creator><creator>Allbee, J</creator><creator>Tuder, R</creator><creator>Woodson, P</creator><creator>Guidot, D M</creator><creator>Rice, G</creator><creator>Singer, J W</creator><creator>Repine, J E</creator><general>The Rockefeller University Press</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>19950201</creationdate><title>Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice</title><author>Abraham, E ; 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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Acyltransferases - antagonists & inhibitors Animals Cell Adhesion Cells, Cultured Chemotaxis, Leukocyte Cytokines - metabolism Hemorrhage - metabolism Humans Inflammation - metabolism Inflammation - pathology Lung - metabolism Lung - pathology Mice Pentoxifylline - analogs & derivatives Pentoxifylline - pharmacology Phosphatidic Acids - metabolism Signal Transduction |
| title | Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice |
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