Integrins as a Primary Signal Transduction Molecule Regulating Monocyte Immediate-Early Gene Induction
Integrins are cell surface receptors found on monocytes that facilitate adhesion to both cellular and extracellular substrates. These integrins are thought to be involved in the selective gene induction observed after monocyte adhesion to various extracellular matrices. To investigate this hypothesi...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1992-10, Vol.89 (19), p.9034-9038 |
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| creator | Yurochko, Andrew D. Liu, David Y. Eierman, David Haskill, Stephen |
| description | Integrins are cell surface receptors found on monocytes that facilitate adhesion to both cellular and extracellular substrates. These integrins are thought to be involved in the selective gene induction observed after monocyte adhesion to various extracellular matrices. To investigate this hypothesis, we stimulated monocytes with monoclonal antibodies to different integrin receptors to specifically mimic the integrin receptor-ligand interactions. Engagement of the common β chain of the β1subfamily of integrins resulted in expression of the inflammatory mediator genes, interleukin 1β, interleukin 1 receptor antagonist, and monocyte adherence-derived inflammatory gene 6 (MAD-6), whereas engagement of the common β chain of the β2family did not. Furthermore, to characterize integrin-mediated gene induction, we examined the ability of antibodies to the α chain of integrin receptors to regulate gene expression. Engagement of the very late antigen 4 (VLA-4) receptor resulted in induction of all the mediator genes. Receptor crosslinking was required because individual Fab fragments were unable to stimulate gene induction whereas the divalent F(ab')2fragment and the whole IgG molecule could. Interleukin 1β secretion was dependent on the anti-integrin antibody used. Some antibodies required a second signal and, for others, direct engagement was sufficient for protein production. In conclusion, engagement of integrin receptors regulated the production of both inflammatory mediator mRNA and protein. These results suggest that integrin-dependent recognition and adherence may provide the key signals for initiation of the inflammatory response during monocyte diapedesis. |
| doi_str_mv | 10.1073/pnas.89.19.9034 |
| format | Article |
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These integrins are thought to be involved in the selective gene induction observed after monocyte adhesion to various extracellular matrices. To investigate this hypothesis, we stimulated monocytes with monoclonal antibodies to different integrin receptors to specifically mimic the integrin receptor-ligand interactions. Engagement of the common β chain of the β1subfamily of integrins resulted in expression of the inflammatory mediator genes, interleukin 1β, interleukin 1 receptor antagonist, and monocyte adherence-derived inflammatory gene 6 (MAD-6), whereas engagement of the common β chain of the β2family did not. Furthermore, to characterize integrin-mediated gene induction, we examined the ability of antibodies to the α chain of integrin receptors to regulate gene expression. Engagement of the very late antigen 4 (VLA-4) receptor resulted in induction of all the mediator genes. Receptor crosslinking was required because individual Fab fragments were unable to stimulate gene induction whereas the divalent F(ab')2fragment and the whole IgG molecule could. Interleukin 1β secretion was dependent on the anti-integrin antibody used. Some antibodies required a second signal and, for others, direct engagement was sufficient for protein production. In conclusion, engagement of integrin receptors regulated the production of both inflammatory mediator mRNA and protein. These results suggest that integrin-dependent recognition and adherence may provide the key signals for initiation of the inflammatory response during monocyte diapedesis.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.89.19.9034</identifier><identifier>PMID: 1384041</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Antibodies ; Antibodies, Monoclonal ; Biological and medical sciences ; Blood ; Blotting, Northern ; Cellular biology ; Crosslinking ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene expression regulation ; Gene Expression Regulation - immunology ; Gene induction ; Genes ; Humans ; Inflammation ; Integrins ; Integrins - physiology ; Interleukin-1 - biosynthesis ; Medical research ; Messenger RNA ; Molecular and cellular biology ; Molecules ; Monocytes ; Monocytes - physiology ; Proteins ; Receptors ; Receptors, Very Late Antigen - physiology ; RNA - genetics ; RNA - isolation & purification ; RNA, Messenger - genetics ; RNA, Messenger - isolation & purification ; Signal Transduction ; T lymphocytes ; Transcriptional Activation</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1992-10, Vol.89 (19), p.9034-9038</ispartof><rights>Copyright 1992 The National Academy of Sciences of the United States of America</rights><rights>1993 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Oct 1, 1992</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c549t-664d6b9a6cd4f62e3037905276a41ecf72c66f8df2c1f9463e319c77801d07ef3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/89/19.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2360326$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2360326$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4407841$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1384041$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yurochko, Andrew D.</creatorcontrib><creatorcontrib>Liu, David Y.</creatorcontrib><creatorcontrib>Eierman, David</creatorcontrib><creatorcontrib>Haskill, Stephen</creatorcontrib><title>Integrins as a Primary Signal Transduction Molecule Regulating Monocyte Immediate-Early Gene Induction</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Integrins are cell surface receptors found on monocytes that facilitate adhesion to both cellular and extracellular substrates. These integrins are thought to be involved in the selective gene induction observed after monocyte adhesion to various extracellular matrices. To investigate this hypothesis, we stimulated monocytes with monoclonal antibodies to different integrin receptors to specifically mimic the integrin receptor-ligand interactions. Engagement of the common β chain of the β1subfamily of integrins resulted in expression of the inflammatory mediator genes, interleukin 1β, interleukin 1 receptor antagonist, and monocyte adherence-derived inflammatory gene 6 (MAD-6), whereas engagement of the common β chain of the β2family did not. Furthermore, to characterize integrin-mediated gene induction, we examined the ability of antibodies to the α chain of integrin receptors to regulate gene expression. Engagement of the very late antigen 4 (VLA-4) receptor resulted in induction of all the mediator genes. Receptor crosslinking was required because individual Fab fragments were unable to stimulate gene induction whereas the divalent F(ab')2fragment and the whole IgG molecule could. Interleukin 1β secretion was dependent on the anti-integrin antibody used. Some antibodies required a second signal and, for others, direct engagement was sufficient for protein production. In conclusion, engagement of integrin receptors regulated the production of both inflammatory mediator mRNA and protein. These results suggest that integrin-dependent recognition and adherence may provide the key signals for initiation of the inflammatory response during monocyte diapedesis.</description><subject>Antibodies</subject><subject>Antibodies, Monoclonal</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Blotting, Northern</subject><subject>Cellular biology</subject><subject>Crosslinking</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene expression regulation</subject><subject>Gene Expression Regulation - immunology</subject><subject>Gene induction</subject><subject>Genes</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Integrins</subject><subject>Integrins - physiology</subject><subject>Interleukin-1 - biosynthesis</subject><subject>Medical research</subject><subject>Messenger RNA</subject><subject>Molecular and cellular biology</subject><subject>Molecules</subject><subject>Monocytes</subject><subject>Monocytes - physiology</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Receptors, Very Late Antigen - physiology</subject><subject>RNA - genetics</subject><subject>RNA - isolation & purification</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - isolation & purification</subject><subject>Signal Transduction</subject><subject>T lymphocytes</subject><subject>Transcriptional Activation</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd1rFDEUxQex1LX67IvKIFKfZnvzMckEfJFS60JF0foc0kyyzpLNbJOMuP-9GWfcqg8KgcA9v3Nzb05RPEGwRMDJ2c6ruGzEEomlAELvFQsEAlWMCrhfLAAwrxqK6YPiYYwbABB1A8fFMSINBYoWhV35ZNah87FU-ZQfQ7dVYV9-7tZeufI6KB_bQaeu9-X73hk9OFN-MuvBqdT5da75Xu-TKVfbrWk7lUx1oYLbl5fG56KfvY-KI6tcNI_n-6T48vbi-vxddfXhcnX-5qrSNRWpYoy27EYopltqGTYECBdQY84URUZbjjVjtmkt1sgKyoghSGjOG0AtcGPJSfF66rsbbvI82vgUlJO7aSvZq07-qfjuq1z332QNUItsP53tob8dTExy20VtnFPe9EOUnOCaCPp_EDHCMOU4gy_-Ajf9EPLXRokBYVYzNnY7myAd-hiDsYeBEcgxZjnGLBshkZBjzNnx7Pc97_gp16y_nHUVtXI2x6i7eMAoBd78xF7N2Nj_l3r3jrSDc8l8T5l8_k8yA08nYBNTHw4EJgwIZuQHncfSxg</recordid><startdate>19921001</startdate><enddate>19921001</enddate><creator>Yurochko, Andrew D.</creator><creator>Liu, David Y.</creator><creator>Eierman, David</creator><creator>Haskill, Stephen</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><scope>IQODW</scope><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>19921001</creationdate><title>Integrins as a Primary Signal Transduction Molecule Regulating Monocyte Immediate-Early Gene Induction</title><author>Yurochko, Andrew D. ; Liu, David Y. ; Eierman, David ; Haskill, Stephen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c549t-664d6b9a6cd4f62e3037905276a41ecf72c66f8df2c1f9463e319c77801d07ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Antibodies</topic><topic>Antibodies, Monoclonal</topic><topic>Biological and medical sciences</topic><topic>Blood</topic><topic>Blotting, Northern</topic><topic>Cellular biology</topic><topic>Crosslinking</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene expression regulation</topic><topic>Gene Expression Regulation - immunology</topic><topic>Gene induction</topic><topic>Genes</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Integrins</topic><topic>Integrins - physiology</topic><topic>Interleukin-1 - biosynthesis</topic><topic>Medical research</topic><topic>Messenger RNA</topic><topic>Molecular and cellular biology</topic><topic>Molecules</topic><topic>Monocytes</topic><topic>Monocytes - physiology</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Receptors, Very Late Antigen - physiology</topic><topic>RNA - genetics</topic><topic>RNA - isolation & purification</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - isolation & purification</topic><topic>Signal Transduction</topic><topic>T lymphocytes</topic><topic>Transcriptional Activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yurochko, Andrew D.</creatorcontrib><creatorcontrib>Liu, David Y.</creatorcontrib><creatorcontrib>Eierman, David</creatorcontrib><creatorcontrib>Haskill, Stephen</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yurochko, Andrew D.</au><au>Liu, David Y.</au><au>Eierman, David</au><au>Haskill, Stephen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrins as a Primary Signal Transduction Molecule Regulating Monocyte Immediate-Early Gene Induction</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1992-10-01</date><risdate>1992</risdate><volume>89</volume><issue>19</issue><spage>9034</spage><epage>9038</epage><pages>9034-9038</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Integrins are cell surface receptors found on monocytes that facilitate adhesion to both cellular and extracellular substrates. These integrins are thought to be involved in the selective gene induction observed after monocyte adhesion to various extracellular matrices. To investigate this hypothesis, we stimulated monocytes with monoclonal antibodies to different integrin receptors to specifically mimic the integrin receptor-ligand interactions. Engagement of the common β chain of the β1subfamily of integrins resulted in expression of the inflammatory mediator genes, interleukin 1β, interleukin 1 receptor antagonist, and monocyte adherence-derived inflammatory gene 6 (MAD-6), whereas engagement of the common β chain of the β2family did not. Furthermore, to characterize integrin-mediated gene induction, we examined the ability of antibodies to the α chain of integrin receptors to regulate gene expression. Engagement of the very late antigen 4 (VLA-4) receptor resulted in induction of all the mediator genes. Receptor crosslinking was required because individual Fab fragments were unable to stimulate gene induction whereas the divalent F(ab')2fragment and the whole IgG molecule could. Interleukin 1β secretion was dependent on the anti-integrin antibody used. Some antibodies required a second signal and, for others, direct engagement was sufficient for protein production. In conclusion, engagement of integrin receptors regulated the production of both inflammatory mediator mRNA and protein. These results suggest that integrin-dependent recognition and adherence may provide the key signals for initiation of the inflammatory response during monocyte diapedesis.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1384041</pmid><doi>10.1073/pnas.89.19.9034</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Antibodies Antibodies, Monoclonal Biological and medical sciences Blood Blotting, Northern Cellular biology Crosslinking Fundamental and applied biological sciences. Psychology Gene Expression Gene expression regulation Gene Expression Regulation - immunology Gene induction Genes Humans Inflammation Integrins Integrins - physiology Interleukin-1 - biosynthesis Medical research Messenger RNA Molecular and cellular biology Molecules Monocytes Monocytes - physiology Proteins Receptors Receptors, Very Late Antigen - physiology RNA - genetics RNA - isolation & purification RNA, Messenger - genetics RNA, Messenger - isolation & purification Signal Transduction T lymphocytes Transcriptional Activation |
| title | Integrins as a Primary Signal Transduction Molecule Regulating Monocyte Immediate-Early Gene Induction |
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