{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T22:10:56Z","timestamp":1682892656753},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2004,12,14]],"date-time":"2004-12-14T00:00:00Z","timestamp":1102982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,12,14]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Haemolytic uraemic syndrome (HUS) is caused by Shiga-toxin-producing Escherichia coli (STEC). Although, Shiga toxin type 2 (Stx2) is responsible for the renal pathogenesis observed in patients, the inflammatory response, including cytokines and polymorphonuclear neutrophils (PMN), plays a key role in the development of HUS. Previously, we demonstrated that Stx2 injection generates an anti-inflammatory reaction characterized by endogenous glucocorticoid (GC) secretion, which attenuates HUS severity in mice. Here, we analysed the effects of Stx2 on the pathogenic function of PMN and the potential role of endogenous GC to limit PMN activation during HUS development in a murine model. For this purpose we assessed the functional activity of isolated PMN after in vivo treatment with Stx2 alone or in simultaneous treatment with Ru486 (GC receptor antagonist). We found that Stx2 increased the generation of reactive oxygen intermediates (ROI) under phobol-myristate-acetate (PMA) stimulation and that the simultaneous treatment with Ru486 strengthened this effect. Conversely, both treatments significantly inhibited in vitro phagocytosis. Furthermore, Stx2 augmented in vitro PMN adhesion to fibrinogen (FGN) and bovine serum albumin (BSA) but not to collagen type I (CTI). Stx2 + Ru486 caused enhanced adhesion to BSA and CTI compared to Stx2. Whereas Stx2 significantly increased migration towards N-formyl-methionyl-leucyl-phenylalanine (fMLP), Stx2 + Ru486 treatment enhanced and accelerated this process. The percentage of apoptotic PMN from Stx2-treated mice was higher compared with controls, but equal to Stx2 + Ru486 treated mice. We conclude that Stx2 activates PMN and that the absence of endogenous GC enhances this activation suggesting that endogenous GC can, at least partially, counteract PMN inflammatory functions.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2005.02659.x","type":"journal-article","created":{"date-parts":[[2004,12,14]],"date-time":"2004-12-14T15:38:59Z","timestamp":1103038739000},"page":"65-73","source":"Crossref","is-referenced-by-count":9,"title":["Endogenous glucocorticoids modulate neutrophil function in a murine model of haemolytic uraemic syndrome"],"prefix":"10.1093","volume":"139","author":[{"given":"S A","family":"G\u00f3mez","sequence":"first","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina"},{"name":"CONICET (Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G C","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina"},{"name":"CONICET (Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Camerano","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Experimental, Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Dran","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Experimental, Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F A","family":"Rosa","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina"},{"name":"CONICET (Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Barrionuevo","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina"},{"name":"CONICET (Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M A","family":"Isturiz","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina"},{"name":"CONICET (Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M S","family":"Palermo","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Hematol\u00f3gicas, Academia Nacional de Medicina"},{"name":"CONICET (Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,12,14]]},"reference":[{"key":"2022010900424844100_b1","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1128\/CMR.11.3.450","article-title":"Pathogenesis and diagnosis of shiga toxin-producing Escherichia coli","volume":"11","author":"Paton","year":"1998","journal-title":"Clin Microbiol Rev"},{"key":"2022010900424844100_b2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1203\/00006450-200108000-00002","article-title":"Pathogenesis of Shiga toxin\u2013associated hemolytic uremic syndrome","volume":"50","author":"Proulx","year":"2001","journal-title":"Pediatr 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