Distinct renal pathology and a chemotactic phenotype after enterohemorrhagic Escherichia coli shiga toxins in non-human primate models of hemolytic uremic syndrome
Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved..
Enterohemorrhagic Escherichia coli cause approximately 1.5 million infections globally with 176,000 cases occurring in the United States annually from ingesting contaminated food, most frequently E. coli O157:H7 in ground beef or fresh produce. In severe cases, the painful prodromal hemorrhagic colitis is complicated by potentially lethal hemolytic uremic syndrome (HUS), particularly in children. Bacterial Shiga-like toxins (Stx1, Stx2) are primarily responsible for HUS and the kidney and neurologic damage that ensue. Small animal models are hampered by the inability to reproduce HUS with thrombotic microangiopathy, hemolytic anemia, and acute kidney injury. Earlier, we showed that nonhuman primates (Papio) recapitulated clinical HUS after Stx challenge and that novel therapeutic intervention rescued the animals. Here, we present detailed light and electron microscopic pathology examination of the kidneys from these Stx studies. Stx1 challenge resulted in more severe glomerular endothelial injury, whereas the glomerular injury after Stx2 also included prominent mesangiolysis and an eosinophilic inflammatory infiltration. Both toxins induced glomerular platelet-rich thrombi, interstitial hemorrhage, and tubular injury. Analysis of kidney and other organs for inflammation biomarkers showed a striking chemotactic profile, with extremely high mRNA levels for IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1α and elevated urine chemokines at 48 hours after challenge. These observations give unique insight into the pathologic consequences of each toxin in a near human setting and present potential pathways for therapeutic intervention.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2013 |
|---|---|
| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:182 |
|---|---|
| Enthalten in: |
The American journal of pathology - 182(2013), 4 vom: 10. Apr., Seite 1227-38 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Stearns-Kurosawa, Deborah J [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Chemokines |
|---|
| Anmerkungen: |
Date Completed 27.08.2013 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ajpath.2012.12.026 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM224963023 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM224963023 | ||
| 003 | DE-627 | ||
| 005 | 20231224064100.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2013 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ajpath.2012.12.026 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0750.xml |
| 035 | |a (DE-627)NLM224963023 | ||
| 035 | |a (NLM)23402998 | ||
| 035 | |a (PII)S0002-9440(13)00036-9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Stearns-Kurosawa, Deborah J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Distinct renal pathology and a chemotactic phenotype after enterohemorrhagic Escherichia coli shiga toxins in non-human primate models of hemolytic uremic syndrome |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.08.2013 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Enterohemorrhagic Escherichia coli cause approximately 1.5 million infections globally with 176,000 cases occurring in the United States annually from ingesting contaminated food, most frequently E. coli O157:H7 in ground beef or fresh produce. In severe cases, the painful prodromal hemorrhagic colitis is complicated by potentially lethal hemolytic uremic syndrome (HUS), particularly in children. Bacterial Shiga-like toxins (Stx1, Stx2) are primarily responsible for HUS and the kidney and neurologic damage that ensue. Small animal models are hampered by the inability to reproduce HUS with thrombotic microangiopathy, hemolytic anemia, and acute kidney injury. Earlier, we showed that nonhuman primates (Papio) recapitulated clinical HUS after Stx challenge and that novel therapeutic intervention rescued the animals. Here, we present detailed light and electron microscopic pathology examination of the kidneys from these Stx studies. Stx1 challenge resulted in more severe glomerular endothelial injury, whereas the glomerular injury after Stx2 also included prominent mesangiolysis and an eosinophilic inflammatory infiltration. Both toxins induced glomerular platelet-rich thrombi, interstitial hemorrhage, and tubular injury. Analysis of kidney and other organs for inflammation biomarkers showed a striking chemotactic profile, with extremely high mRNA levels for IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1α and elevated urine chemokines at 48 hours after challenge. These observations give unique insight into the pathologic consequences of each toxin in a near human setting and present potential pathways for therapeutic intervention | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Chemokines |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Shiga Toxin 1 |2 NLM | |
| 650 | 7 | |a Shiga Toxin 2 |2 NLM | |
| 650 | 7 | |a Shiga Toxins |2 NLM | |
| 700 | 1 | |a Oh, Sun-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Cherla, Rama P |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Moo-Seung |e verfasserin |4 aut | |
| 700 | 1 | |a Tesh, Vernon L |e verfasserin |4 aut | |
| 700 | 1 | |a Papin, James |e verfasserin |4 aut | |
| 700 | 1 | |a Henderson, Joel |e verfasserin |4 aut | |
| 700 | 1 | |a Kurosawa, Shinichiro |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The American journal of pathology |d 1925 |g 182(2013), 4 vom: 10. Apr., Seite 1227-38 |w (DE-627)NLM000077895 |x 1525-2191 |7 nnns |
| 773 | 1 | 8 | |g volume:182 |g year:2013 |g number:4 |g day:10 |g month:04 |g pages:1227-38 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ajpath.2012.12.026 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 182 |j 2013 |e 4 |b 10 |c 04 |h 1227-38 | ||