Effects of IgM from rheumatic fever patients on intracellular calcium levels of neonatal rat cardiac myocytes
Rheumatic fever (RF), a potential sequela of Streptococcus pyogenes pharyngitis, sometimes results in myocarditis and heart failure. Antibodies have been implicated in the pathogenesis of RF and anti-cardiac myosin antibody levels are elevated in RF patients. Since myocarditis is associated with alt...
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| Veröffentlicht in: | Life sciences (1973) 2003-09, Vol.73 (16), p.2101-2111 |
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| container_title | Life sciences (1973) |
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| creator | Bick, Roger J Poindexter, Brian J Tong, Song Kalis, Neale N Van der Merwe, Peter Gatchel, Jennifer Young, David C |
| description | Rheumatic fever (RF), a potential sequela of
Streptococcus pyogenes pharyngitis, sometimes results in myocarditis and heart failure. Antibodies have been implicated in the pathogenesis of RF and anti-cardiac myosin antibody levels are elevated in RF patients. Since myocarditis is associated with altered cardiomyocyte calcium transients it was of interest to determine the direct effects of RF patient antibodies on calcium transients in cultured myocytes.
RF patient polyclonal IgM treatment caused increased calcium retention by neonatal rat heart cells in vitro as determined with isotopically labeled calcium. Therefore, to further characterize this finding, calcium transients were evaluated by real time fluorescence spectroscopy and deconvolution imaging. RF patient polyclonal IgM produced increased calcium retention during the relaxation stage of the contraction cycle leading to a slowing of contraction rate, disorganized calcium transients, and eventual tetany. In contrast, calcium transient studies of cardiomyocytes following treatment with monoclonal anti-myosin antibodies revealed declining intracellular calcium levels, accompanied by disorganized transients and tetany.
Treatment with both antibodies led to myocyte dysfunction and these novel findings suggest a role for antibodies in the pathogenesis of the myocarditis associated with rheumatic carditis. |
| doi_str_mv | 10.1016/S0024-3205(03)00560-5 |
| format | Article |
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Streptococcus pyogenes pharyngitis, sometimes results in myocarditis and heart failure. Antibodies have been implicated in the pathogenesis of RF and anti-cardiac myosin antibody levels are elevated in RF patients. Since myocarditis is associated with altered cardiomyocyte calcium transients it was of interest to determine the direct effects of RF patient antibodies on calcium transients in cultured myocytes.
RF patient polyclonal IgM treatment caused increased calcium retention by neonatal rat heart cells in vitro as determined with isotopically labeled calcium. Therefore, to further characterize this finding, calcium transients were evaluated by real time fluorescence spectroscopy and deconvolution imaging. RF patient polyclonal IgM produced increased calcium retention during the relaxation stage of the contraction cycle leading to a slowing of contraction rate, disorganized calcium transients, and eventual tetany. In contrast, calcium transient studies of cardiomyocytes following treatment with monoclonal anti-myosin antibodies revealed declining intracellular calcium levels, accompanied by disorganized transients and tetany.
Treatment with both antibodies led to myocyte dysfunction and these novel findings suggest a role for antibodies in the pathogenesis of the myocarditis associated with rheumatic carditis.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/S0024-3205(03)00560-5</identifier><identifier>PMID: 12899933</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Animals ; Animals, Newborn ; Antibodies ; Calcium - metabolism ; Calcium channels ; Calcium Channels - immunology ; Calcium Channels - metabolism ; Cells, Cultured ; Fluorescent Antibody Technique, Indirect ; Humans ; Immunoglobulin M - pharmacology ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - pathology ; Rats ; Rheumatic Fever - immunology ; Rheumatic heart disease ; Streptococcus pyogenes</subject><ispartof>Life sciences (1973), 2003-09, Vol.73 (16), p.2101-2111</ispartof><rights>2003 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-1db9059439ceb23c50e0beb6cdb6f90c8095d858bebd42cf9d4e26c5e5a202563</citedby><cites>FETCH-LOGICAL-c425t-1db9059439ceb23c50e0beb6cdb6f90c8095d858bebd42cf9d4e26c5e5a202563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0024-3205(03)00560-5$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12899933$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bick, Roger J</creatorcontrib><creatorcontrib>Poindexter, Brian J</creatorcontrib><creatorcontrib>Tong, Song</creatorcontrib><creatorcontrib>Kalis, Neale N</creatorcontrib><creatorcontrib>Van der Merwe, Peter</creatorcontrib><creatorcontrib>Gatchel, Jennifer</creatorcontrib><creatorcontrib>Young, David C</creatorcontrib><title>Effects of IgM from rheumatic fever patients on intracellular calcium levels of neonatal rat cardiac myocytes</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Rheumatic fever (RF), a potential sequela of
Streptococcus pyogenes pharyngitis, sometimes results in myocarditis and heart failure. Antibodies have been implicated in the pathogenesis of RF and anti-cardiac myosin antibody levels are elevated in RF patients. Since myocarditis is associated with altered cardiomyocyte calcium transients it was of interest to determine the direct effects of RF patient antibodies on calcium transients in cultured myocytes.
RF patient polyclonal IgM treatment caused increased calcium retention by neonatal rat heart cells in vitro as determined with isotopically labeled calcium. Therefore, to further characterize this finding, calcium transients were evaluated by real time fluorescence spectroscopy and deconvolution imaging. RF patient polyclonal IgM produced increased calcium retention during the relaxation stage of the contraction cycle leading to a slowing of contraction rate, disorganized calcium transients, and eventual tetany. In contrast, calcium transient studies of cardiomyocytes following treatment with monoclonal anti-myosin antibodies revealed declining intracellular calcium levels, accompanied by disorganized transients and tetany.
Treatment with both antibodies led to myocyte dysfunction and these novel findings suggest a role for antibodies in the pathogenesis of the myocarditis associated with rheumatic carditis.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Antibodies</subject><subject>Calcium - metabolism</subject><subject>Calcium channels</subject><subject>Calcium Channels - immunology</subject><subject>Calcium Channels - metabolism</subject><subject>Cells, Cultured</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Humans</subject><subject>Immunoglobulin M - pharmacology</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Rats</subject><subject>Rheumatic Fever - immunology</subject><subject>Rheumatic heart disease</subject><subject>Streptococcus pyogenes</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1ERZeFnwDyCZVDytiOnfiEqqqFSkUcgLPl2GMwysdiJ5X239fZXcGNnmzZz7wzmoeQNwwuGTD14RsAryvBQV6AeA8gFVTyGdmwttEVKMGek81f5Jy8zPk3FEo24gU5Z7zVWguxIcNNCOjmTKdA735-oSFNA02_cBnsHB0N-ICJ7sodxxUaaRznZB32_dLbRJ3tXVwG2heuP4SMOI12tj1Ndi7fyUfr6LCf3H7G_IqcBdtnfH06t-TH7c3368_V_ddPd9dX95WruZwr5jsNUtdCO-y4cBIQOuyU850KGlwLWvpWtuXN19wF7WvkykmUlgOXSmzJu2PuLk1_FsyzGWJeh7ZlvCWbRsi65bot4MV_wbJN2dai0U9nskYptcJbIo-gS1POCYPZpTjYtDcMzOrOHNyZVYwBYQ7ujCx1b08Nlm5A_6_qJKsAH49AWTU-REwmu-LFoY-pODR-ik-0eAQL96nb</recordid><startdate>20030905</startdate><enddate>20030905</enddate><creator>Bick, Roger J</creator><creator>Poindexter, Brian J</creator><creator>Tong, Song</creator><creator>Kalis, Neale N</creator><creator>Van der Merwe, Peter</creator><creator>Gatchel, Jennifer</creator><creator>Young, David C</creator><general>Elsevier Inc</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>7QP</scope><scope>7X8</scope></search><sort><creationdate>20030905</creationdate><title>Effects of IgM from rheumatic fever patients on intracellular calcium levels of neonatal rat cardiac myocytes</title><author>Bick, Roger J ; Poindexter, Brian J ; Tong, Song ; Kalis, Neale N ; Van der Merwe, Peter ; Gatchel, Jennifer ; Young, David C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c425t-1db9059439ceb23c50e0beb6cdb6f90c8095d858bebd42cf9d4e26c5e5a202563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Antibodies</topic><topic>Calcium - metabolism</topic><topic>Calcium channels</topic><topic>Calcium Channels - immunology</topic><topic>Calcium Channels - metabolism</topic><topic>Cells, Cultured</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Humans</topic><topic>Immunoglobulin M - pharmacology</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Rats</topic><topic>Rheumatic Fever - immunology</topic><topic>Rheumatic heart disease</topic><topic>Streptococcus pyogenes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bick, Roger J</creatorcontrib><creatorcontrib>Poindexter, Brian J</creatorcontrib><creatorcontrib>Tong, Song</creatorcontrib><creatorcontrib>Kalis, Neale N</creatorcontrib><creatorcontrib>Van der Merwe, Peter</creatorcontrib><creatorcontrib>Gatchel, Jennifer</creatorcontrib><creatorcontrib>Young, David C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bick, Roger J</au><au>Poindexter, Brian J</au><au>Tong, Song</au><au>Kalis, Neale N</au><au>Van der Merwe, Peter</au><au>Gatchel, Jennifer</au><au>Young, David C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of IgM from rheumatic fever patients on intracellular calcium levels of neonatal rat cardiac myocytes</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2003-09-05</date><risdate>2003</risdate><volume>73</volume><issue>16</issue><spage>2101</spage><epage>2111</epage><pages>2101-2111</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Rheumatic fever (RF), a potential sequela of
Streptococcus pyogenes pharyngitis, sometimes results in myocarditis and heart failure. Antibodies have been implicated in the pathogenesis of RF and anti-cardiac myosin antibody levels are elevated in RF patients. Since myocarditis is associated with altered cardiomyocyte calcium transients it was of interest to determine the direct effects of RF patient antibodies on calcium transients in cultured myocytes.
RF patient polyclonal IgM treatment caused increased calcium retention by neonatal rat heart cells in vitro as determined with isotopically labeled calcium. Therefore, to further characterize this finding, calcium transients were evaluated by real time fluorescence spectroscopy and deconvolution imaging. RF patient polyclonal IgM produced increased calcium retention during the relaxation stage of the contraction cycle leading to a slowing of contraction rate, disorganized calcium transients, and eventual tetany. In contrast, calcium transient studies of cardiomyocytes following treatment with monoclonal anti-myosin antibodies revealed declining intracellular calcium levels, accompanied by disorganized transients and tetany.
Treatment with both antibodies led to myocyte dysfunction and these novel findings suggest a role for antibodies in the pathogenesis of the myocarditis associated with rheumatic carditis.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>12899933</pmid><doi>10.1016/S0024-3205(03)00560-5</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals Animals, Newborn Antibodies Calcium - metabolism Calcium channels Calcium Channels - immunology Calcium Channels - metabolism Cells, Cultured Fluorescent Antibody Technique, Indirect Humans Immunoglobulin M - pharmacology Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Rats Rheumatic Fever - immunology Rheumatic heart disease Streptococcus pyogenes |
| title | Effects of IgM from rheumatic fever patients on intracellular calcium levels of neonatal rat cardiac myocytes |
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