{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:31:53Z","timestamp":1772253113973,"version":"3.50.1"},"reference-count":73,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,10,25]],"date-time":"2017-10-25T00:00:00Z","timestamp":1508889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["165\/13"],"award-info":[{"award-number":["165\/13"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L, as consequence of Stx-induced endothelium damage, participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.<\/jats:p>","DOI":"10.3390\/toxins9110331","type":"journal-article","created":{"date-parts":[[2017,10,25]],"date-time":"2017-10-25T11:13:27Z","timestamp":1508930007000},"page":"331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome"],"prefix":"10.3390","volume":"9","author":[{"given":"Maria","family":"Abrey Recalde","sequence":"first","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas-Academia Nacional de Medicina, 1425 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiopatogenia, Departamento de Fisiolog\u00eda, Instituto de Fisiolog\u00eda y Biof\u00edsica \u201cBernardo Houssay\u201d, Facultad de Medicina-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad de Buenos Aires, 1121 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana","family":"Alberto","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n Trombosis, Instituto de investigaciones Hematol\u00f3gicas \u201cMariano R. Castex\u201d, Academia Nacional de Medicina, 1425 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Mejias","sequence":"additional","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas-Academia Nacional de Medicina, 1425 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Ramos","sequence":"additional","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas-Academia Nacional de Medicina, 1425 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Fernandez Brando","sequence":"additional","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas-Academia Nacional de Medicina, 1425 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Bruballa","sequence":"additional","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas-Academia Nacional de Medicina, 1425 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramon","family":"Exeni","sequence":"additional","affiliation":[{"name":"Departamento de Nefrolog\u00eda, Hospital Municipal del Ni\u00f1o, San Justo, B1754FUD Provincia de Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Alconcher","sequence":"additional","affiliation":[{"name":"Unidad de Nefrourolog\u00eda Infantil. Hospital Interzonal General Dr. Jos\u00e9 Penna, Bah\u00eda Blanca, 8000 Provincia de Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Ibarra","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiopatogenia, Departamento de Fisiolog\u00eda, Instituto de Fisiolog\u00eda y Biof\u00edsica \u201cBernardo Houssay\u201d, Facultad de Medicina-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad de Buenos Aires, 1121 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Amaral","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiopatogenia, Departamento de Fisiolog\u00eda, Instituto de Fisiolog\u00eda y Biof\u00edsica \u201cBernardo Houssay\u201d, Facultad de Medicina-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad de Buenos Aires, 1121 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Palermo","sequence":"additional","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas-Academia Nacional de Medicina, 1425 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1586\/eri.09.49","article-title":"Hemolytic uremic syndrome: Pathogenesis and update of interventions","volume":"7","author":"Palermo","year":"2009","journal-title":"Expert Rev. 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