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Thrombin binds to murine bone marrow-derived macrophages and enhances colony-stimulating factor-1-driven mitogenesis
The binding and mitogenic properties of thrombin have been established in various transformed cell lines. In such systems, thrombin induces cell division in the absence of exogenous growth factors, and the enzyme is considered to act directly as a mitogen. This study explores thrombin's interac...
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| Published in: | The Journal of biological chemistry 1990-05, Vol.265 (14), p.7729-7732 |
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| creator | Clohisy, D R Erdmann, J M Wilner, G D |
| description | The binding and mitogenic properties of thrombin have been established in various transformed cell lines. In such systems,
thrombin induces cell division in the absence of exogenous growth factors, and the enzyme is considered to act directly as
a mitogen. This study explores thrombin's interaction with nontransformed, growth factor-dependent cells. Binding of 125I-alpha-thrombin
to colony-stimulating factor (CSF)-1-dependent bone marrow-derived macrophages is saturable, time-dependent, and displaceable
by both unlabeled alpha-thrombin, and esterolytically inactive thrombin. Both dissociation studies of pre-bound radio-labeled
thrombin and Scatchard analysis assisted by the program "Ligand" suggest adherence of thrombin-binding data to a multi-site
model. There are an estimated 2 x 10(4) high affinity sites (Kd = 7 x 10(-9)M) and 2 x 10(6) low affinity sites (Kd = 9 x
10(-7)M) per cell. Quiescent bone marrow-derived macrophages were cultured with either 10(-8)M thrombin, 1000 units of CSF-1/ml,
or both and [3H]thymidine incorporation was determined. Thrombin alone did not induce mitogenesis. CSF-1 induced mitogenesis
with peak [3H] thymidine incorporation occurring 24 h after addition of the mitogen. This CSF-1-dependent mitogenic influence
was enhanced greater than 2-fold by treatment with thrombin. |
| doi_str_mv | 10.1016/S0021-9258(19)38988-4 |
| format | article |
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thrombin induces cell division in the absence of exogenous growth factors, and the enzyme is considered to act directly as
a mitogen. This study explores thrombin's interaction with nontransformed, growth factor-dependent cells. Binding of 125I-alpha-thrombin
to colony-stimulating factor (CSF)-1-dependent bone marrow-derived macrophages is saturable, time-dependent, and displaceable
by both unlabeled alpha-thrombin, and esterolytically inactive thrombin. Both dissociation studies of pre-bound radio-labeled
thrombin and Scatchard analysis assisted by the program "Ligand" suggest adherence of thrombin-binding data to a multi-site
model. There are an estimated 2 x 10(4) high affinity sites (Kd = 7 x 10(-9)M) and 2 x 10(6) low affinity sites (Kd = 9 x
10(-7)M) per cell. Quiescent bone marrow-derived macrophages were cultured with either 10(-8)M thrombin, 1000 units of CSF-1/ml,
or both and [3H]thymidine incorporation was determined. Thrombin alone did not induce mitogenesis. CSF-1 induced mitogenesis
with peak [3H] thymidine incorporation occurring 24 h after addition of the mitogen. This CSF-1-dependent mitogenic influence
was enhanced greater than 2-fold by treatment with thrombin.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(19)38988-4</identifier><identifier>PMID: 2186026</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>AFFINITY ; ANIMAL CELLS ; ANIMAL TISSUES ; ANIMALS ; AZINES ; BASIC BIOLOGICAL SCIENCES ; BETA DECAY RADIOISOTOPES ; BIOCHEMICAL REACTION KINETICS ; BODY ; BONE MARROW ; Bone Marrow Cells ; CELL DIVISION ; Cell Division - drug effects ; COAGULANTS ; COLONY FORMATION ; Colony-Stimulating Factors - pharmacology ; CONNECTIVE TISSUE CELLS ; DAYS LIVING RADIOISOTOPES ; Drug Interactions ; DRUGS ; ELECTRON CAPTURE RADIOISOTOPES ; ENZYMES ; GROWTH FACTORS ; HEMATOLOGIC AGENTS ; HEMATOPOIETIC SYSTEM ; HEMOSTATICS ; HETEROCYCLIC COMPOUNDS ; HYDROGEN COMPOUNDS ; HYDROLASES ; INTERMEDIATE MASS NUCLEI ; IODINE 125 ; IODINE ISOTOPES ; Iodine Radioisotopes ; ISOTOPE APPLICATIONS ; ISOTOPES ; KINETICS ; Macrophage Colony-Stimulating Factor ; MACROPHAGES ; Macrophages - metabolism ; Male ; MAMMALS ; MEMBRANE PROTEINS ; MICE ; Mice, Inbred A ; MITOGENS ; NUCLEI ; NUCLEOSIDES ; NUCLEOTIDES ; ODD-EVEN NUCLEI ; ORGANIC COMPOUNDS ; ORGANIC NITROGEN COMPOUNDS ; ORGANS ; PEPTIDE HYDROLASES ; PHAGOCYTES ; PROTEINS ; PYRIMIDINES ; RADIOISOTOPES ; REACTION KINETICS ; RECEPTORS ; RIBOSIDES ; RODENTS ; SERINE PROTEINASES ; SOMATIC CELLS ; THROMBIN ; Thrombin - metabolism ; Thrombin - pharmacology ; THYMIDINE ; TIME DEPENDENCE ; TISSUES ; TRACER TECHNIQUES ; TRITIUM COMPOUNDS ; VERTEBRATES 550201 -- Biochemistry-- Tracer Techniques</subject><ispartof>The Journal of biological chemistry, 1990-05, Vol.265 (14), p.7729-7732</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-552b04f39a255e7e0981abebb2ce48ea36544db6c7a37aa48d41e8f9d91907ea3</citedby><cites>FETCH-LOGICAL-c406t-552b04f39a255e7e0981abebb2ce48ea36544db6c7a37aa48d41e8f9d91907ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2186026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/6871309$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Clohisy, D R</creatorcontrib><creatorcontrib>Erdmann, J M</creatorcontrib><creatorcontrib>Wilner, G D</creatorcontrib><title>Thrombin binds to murine bone marrow-derived macrophages and enhances colony-stimulating factor-1-driven mitogenesis</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The binding and mitogenic properties of thrombin have been established in various transformed cell lines. In such systems,
thrombin induces cell division in the absence of exogenous growth factors, and the enzyme is considered to act directly as
a mitogen. This study explores thrombin's interaction with nontransformed, growth factor-dependent cells. Binding of 125I-alpha-thrombin
to colony-stimulating factor (CSF)-1-dependent bone marrow-derived macrophages is saturable, time-dependent, and displaceable
by both unlabeled alpha-thrombin, and esterolytically inactive thrombin. Both dissociation studies of pre-bound radio-labeled
thrombin and Scatchard analysis assisted by the program "Ligand" suggest adherence of thrombin-binding data to a multi-site
model. There are an estimated 2 x 10(4) high affinity sites (Kd = 7 x 10(-9)M) and 2 x 10(6) low affinity sites (Kd = 9 x
10(-7)M) per cell. Quiescent bone marrow-derived macrophages were cultured with either 10(-8)M thrombin, 1000 units of CSF-1/ml,
or both and [3H]thymidine incorporation was determined. Thrombin alone did not induce mitogenesis. CSF-1 induced mitogenesis
with peak [3H] thymidine incorporation occurring 24 h after addition of the mitogen. This CSF-1-dependent mitogenic influence
was enhanced greater than 2-fold by treatment with thrombin.</description><subject>AFFINITY</subject><subject>ANIMAL CELLS</subject><subject>ANIMAL TISSUES</subject><subject>ANIMALS</subject><subject>AZINES</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>BETA DECAY RADIOISOTOPES</subject><subject>BIOCHEMICAL REACTION KINETICS</subject><subject>BODY</subject><subject>BONE MARROW</subject><subject>Bone Marrow Cells</subject><subject>CELL DIVISION</subject><subject>Cell Division - drug effects</subject><subject>COAGULANTS</subject><subject>COLONY FORMATION</subject><subject>Colony-Stimulating Factors - pharmacology</subject><subject>CONNECTIVE TISSUE CELLS</subject><subject>DAYS LIVING RADIOISOTOPES</subject><subject>Drug Interactions</subject><subject>DRUGS</subject><subject>ELECTRON CAPTURE RADIOISOTOPES</subject><subject>ENZYMES</subject><subject>GROWTH FACTORS</subject><subject>HEMATOLOGIC AGENTS</subject><subject>HEMATOPOIETIC SYSTEM</subject><subject>HEMOSTATICS</subject><subject>HETEROCYCLIC COMPOUNDS</subject><subject>HYDROGEN COMPOUNDS</subject><subject>HYDROLASES</subject><subject>INTERMEDIATE MASS NUCLEI</subject><subject>IODINE 125</subject><subject>IODINE ISOTOPES</subject><subject>Iodine Radioisotopes</subject><subject>ISOTOPE APPLICATIONS</subject><subject>ISOTOPES</subject><subject>KINETICS</subject><subject>Macrophage Colony-Stimulating Factor</subject><subject>MACROPHAGES</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>MAMMALS</subject><subject>MEMBRANE PROTEINS</subject><subject>MICE</subject><subject>Mice, Inbred A</subject><subject>MITOGENS</subject><subject>NUCLEI</subject><subject>NUCLEOSIDES</subject><subject>NUCLEOTIDES</subject><subject>ODD-EVEN NUCLEI</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANIC NITROGEN COMPOUNDS</subject><subject>ORGANS</subject><subject>PEPTIDE HYDROLASES</subject><subject>PHAGOCYTES</subject><subject>PROTEINS</subject><subject>PYRIMIDINES</subject><subject>RADIOISOTOPES</subject><subject>REACTION KINETICS</subject><subject>RECEPTORS</subject><subject>RIBOSIDES</subject><subject>RODENTS</subject><subject>SERINE PROTEINASES</subject><subject>SOMATIC CELLS</subject><subject>THROMBIN</subject><subject>Thrombin - metabolism</subject><subject>Thrombin - pharmacology</subject><subject>THYMIDINE</subject><subject>TIME DEPENDENCE</subject><subject>TISSUES</subject><subject>TRACER TECHNIQUES</subject><subject>TRITIUM COMPOUNDS</subject><subject>VERTEBRATES 550201 -- Biochemistry-- Tracer Techniques</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><recordid>eNo9kF9LHDEUxUOp2K3tRxAG-9I-RJNMMpM8ithWEHxQoW8hf-7spOwkS5JV_PZmXTFwEy7nnHDvD6FTSs4pocPFPSGMYsWE_EnVr14qKTH_hFaUyB73gv77jFYfli_oayn_STtc0WN0zKgcCBtWqD7MOS02xK6VL11N3bLLIUJnU7sWk3N6xh5yeALfWpfTdjZrKJ2JvoM4m-ha49ImxRdcalh2G1NDXHeTcTVlTLHfZ2O3hJrWEKGE8g0dTWZT4Pv7e4Ief18_XP3Ft3d_bq4ub7HjZKhYCGYJn3plmBAwAlGSGgvWMgdcgukHwbm3gxtNPxrDpecU5KS8ooqMTT9BZ4d_UxtMFxcquNmlGMFVPciR9kQ1kziY2mqlZJj0Noe294umRO9J6zfSeo9RU6XfSGvecqeH3HZnF_AfqXe0Tf9x0Oewnp9DBm1DcjMsmg1CU67Hkan-FUKUh58</recordid><startdate>19900515</startdate><enddate>19900515</enddate><creator>Clohisy, D R</creator><creator>Erdmann, J M</creator><creator>Wilner, G D</creator><general>American Society for Biochemistry and Molecular 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>OTOTI</scope></search><sort><creationdate>19900515</creationdate><title>Thrombin binds to murine bone marrow-derived macrophages and enhances colony-stimulating factor-1-driven mitogenesis</title><author>Clohisy, D R ; Erdmann, J M ; Wilner, G D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-552b04f39a255e7e0981abebb2ce48ea36544db6c7a37aa48d41e8f9d91907ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>AFFINITY</topic><topic>ANIMAL CELLS</topic><topic>ANIMAL TISSUES</topic><topic>ANIMALS</topic><topic>AZINES</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>BETA DECAY RADIOISOTOPES</topic><topic>BIOCHEMICAL REACTION KINETICS</topic><topic>BODY</topic><topic>BONE MARROW</topic><topic>Bone Marrow Cells</topic><topic>CELL DIVISION</topic><topic>Cell Division - drug effects</topic><topic>COAGULANTS</topic><topic>COLONY FORMATION</topic><topic>Colony-Stimulating Factors - pharmacology</topic><topic>CONNECTIVE TISSUE CELLS</topic><topic>DAYS LIVING RADIOISOTOPES</topic><topic>Drug Interactions</topic><topic>DRUGS</topic><topic>ELECTRON CAPTURE RADIOISOTOPES</topic><topic>ENZYMES</topic><topic>GROWTH FACTORS</topic><topic>HEMATOLOGIC AGENTS</topic><topic>HEMATOPOIETIC SYSTEM</topic><topic>HEMOSTATICS</topic><topic>HETEROCYCLIC COMPOUNDS</topic><topic>HYDROGEN COMPOUNDS</topic><topic>HYDROLASES</topic><topic>INTERMEDIATE MASS NUCLEI</topic><topic>IODINE 125</topic><topic>IODINE ISOTOPES</topic><topic>Iodine Radioisotopes</topic><topic>ISOTOPE APPLICATIONS</topic><topic>ISOTOPES</topic><topic>KINETICS</topic><topic>Macrophage Colony-Stimulating Factor</topic><topic>MACROPHAGES</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>MAMMALS</topic><topic>MEMBRANE PROTEINS</topic><topic>MICE</topic><topic>Mice, Inbred A</topic><topic>MITOGENS</topic><topic>NUCLEI</topic><topic>NUCLEOSIDES</topic><topic>NUCLEOTIDES</topic><topic>ODD-EVEN NUCLEI</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANIC NITROGEN COMPOUNDS</topic><topic>ORGANS</topic><topic>PEPTIDE HYDROLASES</topic><topic>PHAGOCYTES</topic><topic>PROTEINS</topic><topic>PYRIMIDINES</topic><topic>RADIOISOTOPES</topic><topic>REACTION KINETICS</topic><topic>RECEPTORS</topic><topic>RIBOSIDES</topic><topic>RODENTS</topic><topic>SERINE PROTEINASES</topic><topic>SOMATIC CELLS</topic><topic>THROMBIN</topic><topic>Thrombin - metabolism</topic><topic>Thrombin - pharmacology</topic><topic>THYMIDINE</topic><topic>TIME DEPENDENCE</topic><topic>TISSUES</topic><topic>TRACER TECHNIQUES</topic><topic>TRITIUM COMPOUNDS</topic><topic>VERTEBRATES 550201 -- Biochemistry-- Tracer Techniques</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Clohisy, D R</creatorcontrib><creatorcontrib>Erdmann, J M</creatorcontrib><creatorcontrib>Wilner, G D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Clohisy, D R</au><au>Erdmann, J M</au><au>Wilner, G D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thrombin binds to murine bone marrow-derived macrophages and enhances colony-stimulating factor-1-driven mitogenesis</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1990-05-15</date><risdate>1990</risdate><volume>265</volume><issue>14</issue><spage>7729</spage><epage>7732</epage><pages>7729-7732</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The binding and mitogenic properties of thrombin have been established in various transformed cell lines. In such systems,
thrombin induces cell division in the absence of exogenous growth factors, and the enzyme is considered to act directly as
a mitogen. This study explores thrombin's interaction with nontransformed, growth factor-dependent cells. Binding of 125I-alpha-thrombin
to colony-stimulating factor (CSF)-1-dependent bone marrow-derived macrophages is saturable, time-dependent, and displaceable
by both unlabeled alpha-thrombin, and esterolytically inactive thrombin. Both dissociation studies of pre-bound radio-labeled
thrombin and Scatchard analysis assisted by the program "Ligand" suggest adherence of thrombin-binding data to a multi-site
model. There are an estimated 2 x 10(4) high affinity sites (Kd = 7 x 10(-9)M) and 2 x 10(6) low affinity sites (Kd = 9 x
10(-7)M) per cell. Quiescent bone marrow-derived macrophages were cultured with either 10(-8)M thrombin, 1000 units of CSF-1/ml,
or both and [3H]thymidine incorporation was determined. Thrombin alone did not induce mitogenesis. CSF-1 induced mitogenesis
with peak [3H] thymidine incorporation occurring 24 h after addition of the mitogen. This CSF-1-dependent mitogenic influence
was enhanced greater than 2-fold by treatment with thrombin.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>2186026</pmid><doi>10.1016/S0021-9258(19)38988-4</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 1990-05, Vol.265 (14), p.7729-7732 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_osti_scitechconnect_6871309 |
| source | ScienceDirect Journals |
| subjects | AFFINITY ANIMAL CELLS ANIMAL TISSUES ANIMALS AZINES BASIC BIOLOGICAL SCIENCES BETA DECAY RADIOISOTOPES BIOCHEMICAL REACTION KINETICS BODY BONE MARROW Bone Marrow Cells CELL DIVISION Cell Division - drug effects COAGULANTS COLONY FORMATION Colony-Stimulating Factors - pharmacology CONNECTIVE TISSUE CELLS DAYS LIVING RADIOISOTOPES Drug Interactions DRUGS ELECTRON CAPTURE RADIOISOTOPES ENZYMES GROWTH FACTORS HEMATOLOGIC AGENTS HEMATOPOIETIC SYSTEM HEMOSTATICS HETEROCYCLIC COMPOUNDS HYDROGEN COMPOUNDS HYDROLASES INTERMEDIATE MASS NUCLEI IODINE 125 IODINE ISOTOPES Iodine Radioisotopes ISOTOPE APPLICATIONS ISOTOPES KINETICS Macrophage Colony-Stimulating Factor MACROPHAGES Macrophages - metabolism Male MAMMALS MEMBRANE PROTEINS MICE Mice, Inbred A MITOGENS NUCLEI NUCLEOSIDES NUCLEOTIDES ODD-EVEN NUCLEI ORGANIC COMPOUNDS ORGANIC NITROGEN COMPOUNDS ORGANS PEPTIDE HYDROLASES PHAGOCYTES PROTEINS PYRIMIDINES RADIOISOTOPES REACTION KINETICS RECEPTORS RIBOSIDES RODENTS SERINE PROTEINASES SOMATIC CELLS THROMBIN Thrombin - metabolism Thrombin - pharmacology THYMIDINE TIME DEPENDENCE TISSUES TRACER TECHNIQUES TRITIUM COMPOUNDS VERTEBRATES 550201 -- Biochemistry-- Tracer Techniques |
| title | Thrombin binds to murine bone marrow-derived macrophages and enhances colony-stimulating factor-1-driven mitogenesis |
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