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STI571 inhibits growth and adhesion of human mast cells in culture
Stem cell factor (SCF)/c‐kit system is critical for human mast cell development. We thus examined the effects of STI571, an inhibitor of the c‐kit tyrosine kinase receptor, on the proliferation and function of human mast cells. STI571 at concentrations of 10−6 M or higher almost completely abolished...
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| Published in: | Journal of leukocyte biology 2003-12, Vol.74 (6), p.1026-1034 |
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| Main Authors: | , , , , , , , , , , , , |
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| Language: | English |
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| container_end_page | 1034 |
| container_issue | 6 |
| container_start_page | 1026 |
| container_title | Journal of leukocyte biology |
| container_volume | 74 |
| creator | Takeuchi, Kouichi Koike, Kenichi Kamijo, Takehiko Ishida, Shuichi Nakazawa, Yozo Kurokawa, Yumi Sakashita, Kazuo Kinoshita, Tatsuya Matsuzawa, Shigeyuki Shiohara, Masaaki Yamashita, Tetsuji Nakajima, Motowo Komiyama, Atsushi |
| description | Stem cell factor (SCF)/c‐kit system is critical for human mast cell development. We thus examined the effects of STI571, an inhibitor of the c‐kit tyrosine kinase receptor, on the proliferation and function of human mast cells. STI571 at concentrations of 10−6 M or higher almost completely abolished the SCF‐dependent progeny generation from cord blood‐derived cultured mast cells through an inhibition of the tyrosine phosphorylation of c‐kit. The compound also suppressed the early phase of mast cell development. The extinction of mast cell growth induced by STI571 may be due largely to apoptosis according to the flow cytometric analysis and gel electrophoresis. Two‐hour exposure to STI571 that failed to influence the total viable cell number suppressed adhesion of the cells to fibronectin in the presence of SCF without altering the expressions of integrin molecules. Our results may provide a fundamental insight for the clinical application of STI571 in allergic disorders. |
| doi_str_mv | 10.1189/jlb.0602284 |
| format | article |
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We thus examined the effects of STI571, an inhibitor of the c‐kit tyrosine kinase receptor, on the proliferation and function of human mast cells. STI571 at concentrations of 10−6 M or higher almost completely abolished the SCF‐dependent progeny generation from cord blood‐derived cultured mast cells through an inhibition of the tyrosine phosphorylation of c‐kit. The compound also suppressed the early phase of mast cell development. The extinction of mast cell growth induced by STI571 may be due largely to apoptosis according to the flow cytometric analysis and gel electrophoresis. Two‐hour exposure to STI571 that failed to influence the total viable cell number suppressed adhesion of the cells to fibronectin in the presence of SCF without altering the expressions of integrin molecules. Our results may provide a fundamental insight for the clinical application of STI571 in allergic disorders.</description><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1189/jlb.0602284</identifier><identifier>PMID: 12960256</identifier><language>eng</language><publisher>United States: Society for Leukocyte Biology</publisher><subject>Antigens, CD - metabolism ; Apoptosis - drug effects ; Benzamides ; CD34+ cells ; Cell Adhesion - drug effects ; Cell Division - drug effects ; Cells, Cultured ; cord blood ; c‐kit ; Drug Combinations ; Enzyme Inhibitors - pharmacology ; Female ; Fetal Blood - drug effects ; Fetal Blood - metabolism ; Fibronectins - pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology ; Humans ; Imatinib Mesylate ; Infant, Newborn ; Mast Cells - cytology ; Mast Cells - metabolism ; Phosphorylation ; Piperazines - pharmacology ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Proto-Oncogene Proteins c-kit - metabolism ; Pyrimidines - pharmacology ; stem cell factor ; Tyrosine - metabolism</subject><ispartof>Journal of leukocyte biology, 2003-12, Vol.74 (6), p.1026-1034</ispartof><rights>2003 Society for Leukocyte Biology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4236-82253545697bbbc6fed7cf6edcc0ce2667d3bf5eff4f3da57d666c6e93cd68df3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1189%2Fjlb.0602284$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1189%2Fjlb.0602284$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12960256$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takeuchi, Kouichi</creatorcontrib><creatorcontrib>Koike, Kenichi</creatorcontrib><creatorcontrib>Kamijo, Takehiko</creatorcontrib><creatorcontrib>Ishida, Shuichi</creatorcontrib><creatorcontrib>Nakazawa, Yozo</creatorcontrib><creatorcontrib>Kurokawa, Yumi</creatorcontrib><creatorcontrib>Sakashita, Kazuo</creatorcontrib><creatorcontrib>Kinoshita, Tatsuya</creatorcontrib><creatorcontrib>Matsuzawa, Shigeyuki</creatorcontrib><creatorcontrib>Shiohara, Masaaki</creatorcontrib><creatorcontrib>Yamashita, Tetsuji</creatorcontrib><creatorcontrib>Nakajima, Motowo</creatorcontrib><creatorcontrib>Komiyama, Atsushi</creatorcontrib><title>STI571 inhibits growth and adhesion of human mast cells in culture</title><title>Journal of leukocyte biology</title><addtitle>J Leukoc Biol</addtitle><description>Stem cell factor (SCF)/c‐kit system is critical for human mast cell development. We thus examined the effects of STI571, an inhibitor of the c‐kit tyrosine kinase receptor, on the proliferation and function of human mast cells. STI571 at concentrations of 10−6 M or higher almost completely abolished the SCF‐dependent progeny generation from cord blood‐derived cultured mast cells through an inhibition of the tyrosine phosphorylation of c‐kit. The compound also suppressed the early phase of mast cell development. The extinction of mast cell growth induced by STI571 may be due largely to apoptosis according to the flow cytometric analysis and gel electrophoresis. Two‐hour exposure to STI571 that failed to influence the total viable cell number suppressed adhesion of the cells to fibronectin in the presence of SCF without altering the expressions of integrin molecules. Our results may provide a fundamental insight for the clinical application of STI571 in allergic disorders.</description><subject>Antigens, CD - metabolism</subject><subject>Apoptosis - drug effects</subject><subject>Benzamides</subject><subject>CD34+ cells</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Division - drug effects</subject><subject>Cells, Cultured</subject><subject>cord blood</subject><subject>c‐kit</subject><subject>Drug Combinations</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>Fetal Blood - drug effects</subject><subject>Fetal Blood - metabolism</subject><subject>Fibronectins - pharmacology</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology</subject><subject>Humans</subject><subject>Imatinib Mesylate</subject><subject>Infant, Newborn</subject><subject>Mast Cells - cytology</subject><subject>Mast Cells - metabolism</subject><subject>Phosphorylation</subject><subject>Piperazines - pharmacology</subject><subject>Protein-Tyrosine Kinases - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-kit - metabolism</subject><subject>Pyrimidines - pharmacology</subject><subject>stem cell factor</subject><subject>Tyrosine - metabolism</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqFkDtPwzAUhS0EgvKY2JEnFhTwK9fJSCueqsQAzJbjBzHKo8SJov57UlqJDaa7fOfcow-hc0quKc3ym8-quCZAGMvEHprRnGcJB8n30YxIQZNUEHKEjmP8JIRwBuQQHVGWT4EUZmj--vaUSopDU4Yi9BF_dO3Yl1g3FmtbuhjaBrcel0OtG1zr2GPjqipOAWyGqh86d4oOvK6iO9vdE_R-f_e2eEyWLw9Pi9tlYgTjkGSMpTwVKeSyKAoD3llpPDhrDDGOAUjLC58674XnVqfSAoABl3NjIbOen6DLbe-qa78GF3tVh7gZoxvXDlFJKngmQPwL0pxBThmdwKstaLo2xs55tepCrbu1okRt3KrJrdq5neiLXe1Q1M7-sjuZE0C2wBgqt_6rSz0v55Qw-J1aho9yDJ1TsdZVNX1gahxHKRSoH_AbCS2QJw</recordid><startdate>200312</startdate><enddate>200312</enddate><creator>Takeuchi, Kouichi</creator><creator>Koike, Kenichi</creator><creator>Kamijo, Takehiko</creator><creator>Ishida, Shuichi</creator><creator>Nakazawa, Yozo</creator><creator>Kurokawa, Yumi</creator><creator>Sakashita, Kazuo</creator><creator>Kinoshita, Tatsuya</creator><creator>Matsuzawa, Shigeyuki</creator><creator>Shiohara, Masaaki</creator><creator>Yamashita, Tetsuji</creator><creator>Nakajima, Motowo</creator><creator>Komiyama, Atsushi</creator><general>Society for Leukocyte Biology</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></search><sort><creationdate>200312</creationdate><title>STI571 inhibits growth and adhesion of human mast cells in culture</title><author>Takeuchi, Kouichi ; Koike, Kenichi ; Kamijo, Takehiko ; Ishida, Shuichi ; Nakazawa, Yozo ; Kurokawa, Yumi ; Sakashita, Kazuo ; Kinoshita, Tatsuya ; Matsuzawa, Shigeyuki ; Shiohara, Masaaki ; Yamashita, Tetsuji ; Nakajima, Motowo ; Komiyama, Atsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4236-82253545697bbbc6fed7cf6edcc0ce2667d3bf5eff4f3da57d666c6e93cd68df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Antigens, CD - metabolism</topic><topic>Apoptosis - drug effects</topic><topic>Benzamides</topic><topic>CD34+ cells</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Division - drug effects</topic><topic>Cells, Cultured</topic><topic>cord blood</topic><topic>c‐kit</topic><topic>Drug Combinations</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>Fetal Blood - drug effects</topic><topic>Fetal Blood - metabolism</topic><topic>Fibronectins - pharmacology</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology</topic><topic>Humans</topic><topic>Imatinib Mesylate</topic><topic>Infant, Newborn</topic><topic>Mast Cells - cytology</topic><topic>Mast Cells - metabolism</topic><topic>Phosphorylation</topic><topic>Piperazines - pharmacology</topic><topic>Protein-Tyrosine Kinases - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-kit - metabolism</topic><topic>Pyrimidines - pharmacology</topic><topic>stem cell factor</topic><topic>Tyrosine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takeuchi, Kouichi</creatorcontrib><creatorcontrib>Koike, Kenichi</creatorcontrib><creatorcontrib>Kamijo, Takehiko</creatorcontrib><creatorcontrib>Ishida, Shuichi</creatorcontrib><creatorcontrib>Nakazawa, Yozo</creatorcontrib><creatorcontrib>Kurokawa, Yumi</creatorcontrib><creatorcontrib>Sakashita, Kazuo</creatorcontrib><creatorcontrib>Kinoshita, Tatsuya</creatorcontrib><creatorcontrib>Matsuzawa, Shigeyuki</creatorcontrib><creatorcontrib>Shiohara, Masaaki</creatorcontrib><creatorcontrib>Yamashita, Tetsuji</creatorcontrib><creatorcontrib>Nakajima, Motowo</creatorcontrib><creatorcontrib>Komiyama, Atsushi</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>MEDLINE - Academic</collection><jtitle>Journal of leukocyte biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takeuchi, Kouichi</au><au>Koike, Kenichi</au><au>Kamijo, Takehiko</au><au>Ishida, Shuichi</au><au>Nakazawa, Yozo</au><au>Kurokawa, Yumi</au><au>Sakashita, Kazuo</au><au>Kinoshita, Tatsuya</au><au>Matsuzawa, Shigeyuki</au><au>Shiohara, Masaaki</au><au>Yamashita, Tetsuji</au><au>Nakajima, Motowo</au><au>Komiyama, Atsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>STI571 inhibits growth and adhesion of human mast cells in culture</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2003-12</date><risdate>2003</risdate><volume>74</volume><issue>6</issue><spage>1026</spage><epage>1034</epage><pages>1026-1034</pages><issn>0741-5400</issn><eissn>1938-3673</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><notes>ObjectType-Article-1</notes><notes>ObjectType-Feature-2</notes><abstract>Stem cell factor (SCF)/c‐kit system is critical for human mast cell development. We thus examined the effects of STI571, an inhibitor of the c‐kit tyrosine kinase receptor, on the proliferation and function of human mast cells. STI571 at concentrations of 10−6 M or higher almost completely abolished the SCF‐dependent progeny generation from cord blood‐derived cultured mast cells through an inhibition of the tyrosine phosphorylation of c‐kit. The compound also suppressed the early phase of mast cell development. The extinction of mast cell growth induced by STI571 may be due largely to apoptosis according to the flow cytometric analysis and gel electrophoresis. Two‐hour exposure to STI571 that failed to influence the total viable cell number suppressed adhesion of the cells to fibronectin in the presence of SCF without altering the expressions of integrin molecules. Our results may provide a fundamental insight for the clinical application of STI571 in allergic disorders.</abstract><cop>United States</cop><pub>Society for Leukocyte Biology</pub><pmid>12960256</pmid><doi>10.1189/jlb.0602284</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of leukocyte biology, 2003-12, Vol.74 (6), p.1026-1034 |
| issn | 0741-5400 1938-3673 |
| language | eng |
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| source | Wiley-Blackwell Journals; Oxford University Press Journals |
| subjects | Antigens, CD - metabolism Apoptosis - drug effects Benzamides CD34+ cells Cell Adhesion - drug effects Cell Division - drug effects Cells, Cultured cord blood c‐kit Drug Combinations Enzyme Inhibitors - pharmacology Female Fetal Blood - drug effects Fetal Blood - metabolism Fibronectins - pharmacology Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology Humans Imatinib Mesylate Infant, Newborn Mast Cells - cytology Mast Cells - metabolism Phosphorylation Piperazines - pharmacology Protein-Tyrosine Kinases - antagonists & inhibitors Proto-Oncogene Proteins c-kit - metabolism Pyrimidines - pharmacology stem cell factor Tyrosine - metabolism |
| title | STI571 inhibits growth and adhesion of human mast cells in culture |
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