CoChat
Sign Up
Cited by 135

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Dysfunctional expansion of hematopoietic stem cells and block of myeloid differentiation in lethal sepsis

Rodriguez, Sonia, Chora, Angelo, Goumnerov, Boyan, Mumaw, Christen, Goebel, W. Scott, Fernandez, Luis, Baydoun, Hasan, HogenEsch, Harm, Dombkowski, David M., Karlewicz, Carol A., Rice, Susan, Rahme, Laurence G., Carlesso, Nadia·2009·Blood
DOI 10.1182/blood-2009-04-214916
Open this paper in CoChat — free account

Abstract

Severe sepsis is one of the leading causes of death worldwide. High mortality rates in sepsis are frequently associated with neutropenia. Despite the central role of neutrophils in innate immunity, the mechanisms causing neutropenia during sepsis remain elusive. Here, we show that neutropenia is caused in part by apoptosis and is sustained by a block of hematopoietic stem cell (HSC) differentiation. Using a sepsis murine model, we found that the human opportunistic bacterial pathogen Pseudomonas aeruginosa caused neutrophil depletion and expansion of the HSC pool in the bone marrow. “Septic” HSCs were significantly impaired in competitive repopulation assays and defective in generating common myeloid progenitors and granulocyte-monocyte progenitors, resulting in lower rates of myeloid differentiation in vitro and in vivo. Delayed myeloid-neutrophil differentiation was further mapped using a lysozyme–green fluorescent protein (GFP) reporter mouse. Pseudomonas's lipopolysaccharide was necessary and sufficient to induce myelosuppresion and required intact TLR4 signaling. Our results establish a previously unrecognized link between HSC regulation and host response in severe sepsis and demonstrate a novel role for TLR4.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1182/blood-2009-04-214916

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 33

  1. Hotchkiss, 2003, The pathophysiology and treatment of sepsis., N Engl J Med, 348, 138, 10.1056/NEJMra021333 · DOI
  2. Blank, 2008, Signaling pathways governing stem-cell fate., Blood, 111, 492, 10.1182/blood-2007-07-075168 · DOI
  3. Scadden, 2006, The stem-cell niche as an entity of action., Nature, 441, 1075, 10.1038/nature04957 · DOI
  4. Riedemann, 2003, Novel strategies for the treatment of sepsis., Nat Med, 9, 517, 10.1038/nm0503-517 · DOI
  5. Rahme, 1995, Common virulence factors for bacterial pathogenicity in plants and animals., Science, 268, 1899, 10.1126/science.7604262 · DOI
  6. Stevenson, 2003, A mouse model of burn wounding and sepsis., Methods Mol Med, 78, 95
  7. Faust, 2000, Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages., Blood, 96, 719, 10.1182/blood.V96.2.719 · DOI
  8. Cheng, 2000, Hematopoietic stem cell quiescence maintained by p21cip1/waf1., Science, 287, 1804, 10.1126/science.287.5459.1804 · DOI · Paper page
  9. Ploemacher, 1989, An in vitro limiting-dilution assay of long-term repopulating hematopoietic stem cells in the mouse., Blood, 74, 2755, 10.1182/blood.V74.8.2755.2755 · DOI
  10. Shoup, 1998, Mechanisms of neutropenia involving myeloid maturation arrest in burn sepsis., Ann Surg, 228, 112, 10.1097/00000658-199807000-00017 · DOI
  11. Rittirsch, 2008, Harmful molecular mechanisms in sepsis., Nat Rev Immunol, 8, 776, 10.1038/nri2402 · DOI
  12. Morrison, 1994, The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype., Immunity, 1, 661, 10.1016/1074-7613(94)90037-X · DOI
  13. Rahme, 1997, Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors., Proc Natl Acad Sci U S A, 94, 13245, 10.1073/pnas.94.24.13245 · DOI
  14. Roy, 2007, Pathogen subversion of cell-intrinsic innate immunity., Nat Immunol, 8, 1179, 10.1038/ni1528 · DOI
  15. Sarmento, 2005, Notch1 modulates timing of G1-S progression by inducing SKP2 transcription and p27Kip1 degradation., J Exp Med, 202, 157, 10.1084/jem.20050559 · DOI
  16. Nagai, 2006, Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment., Immunity, 24, 801, 10.1016/j.immuni.2006.04.008 · DOI
  17. Liang, 2005, Bacterial peptidoglycan-associated lipoprotein: a naturally occurring toll-like receptor 2 agonist that is shed into serum and has synergy with lipopolysaccharide., J Infect Dis, 191, 939, 10.1086/427815 · DOI
  18. Rittirsch, 2007, The disconnect between animal models of sepsis and human sepsis., J Leukoc Biol, 81, 137, 10.1189/jlb.0806542 · DOI
  19. Stevens, 1994, A quantitative model of invasive Pseudomonas infection in burn injury., J Burn Care Rehabil, 15, 232, 10.1097/00004630-199405000-00005 · DOI
  20. Rios-Santos, 2007, Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide., Am J Respir Crit Care Med, 175, 490, 10.1164/rccm.200601-103OC · DOI
  21. Zantl, 1998, Essential role of gamma interferon in survival of colon ascendens stent peritonitis, a novel murine model of abdominal sepsis., Infect Immun, 66, 2300, 10.1128/IAI.66.5.2300-2309.1998 · DOI
  22. Delano, 2007, MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis., J Exp Med, 204, 1463, 10.1084/jem.20062602 · DOI
  23. Feng, 2008, The p47 GTPase Lrg-47 (Irgm1) links host defense and hematopoietic stem cell proliferation., Cell Stem Cell, 2, 83, 10.1016/j.stem.2007.10.007 · DOI
  24. Silva, 2001, Bone marrow stem cell and progenitor response to injury., Wound Repair Regen, 9, 495, 10.1046/j.1524-475x.2001.00495.x · DOI
  25. Bou Ghanem, 2009, Multiple mechanisms contribute to the robust rapid gamma interferon response by CD8+ T cells during Listeria monocytogenes infection., Infect Immun, 77, 1492, 10.1128/IAI.01207-08 · DOI
  26. Park, 2004, Anthrolysin O and other gram-positive cytolysins are toll-like receptor 4 agonists., J Exp Med, 200, 1647, 10.1084/jem.20041215 · DOI
  27. Zhu, 2009, B7-H4–deficient mice display augmented neutrophil-mediated innate immunity., Blood, 113, 1759, 10.1182/blood-2008-01-133223 · DOI
  28. Degowin, 1985, Chronic inflammation impairs hematopoiesis and survival after irradiation., J Lab Clin Med, 105, 299
  29. Santangelo, 2001, Myeloid commitment shifts toward monocytopoiesis after thermal injury and sepsis., Ann Surg, 233, 97, 10.1097/00000658-200101000-00015 · DOI
  30. Liu, 2009, p53 regulates hematopoietic stem cell quiescence., Cell Stem Cell, 4, 37, 10.1016/j.stem.2008.11.006 · DOI · Paper page
  31. Viale, 2009, Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells., Nature, 457, 51, 10.1038/nature07618 · DOI
  32. Corey, 2007, Myelodysplastic syndromes: the complexity of stem-cell diseases., Nat Rev Cancer, 7, 118, 10.1038/nrc2047 · DOI
  33. BitMansour, 2002, Myeloid progenitors protect against invasive aspergillosis and Pseudomonas aeruginosa infection following hematopoietic stem cell transplantation., Blood, 100, 4660, 10.1182/blood-2002-05-1552 · DOI

Cited by

See all 135

Metadata

Authors
Rodriguez, S., Chora, A., Goumnerov, B., Mumaw, C., Goebel, W. S., Fernandez, L., Baydoun, H., HogenEsch, H., Dombkowski, D. M., Karlewicz, C. A., Rice, S., Rahme, L. G., & Carlesso, N.
Affiliations
  • Herman B Wells Center, Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis;
  • Massachusetts General Hospital, Harvard Medical School, Boston;
  • Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN
Venue
Blood
Publisher
American Society of Hematology
Published
2009-11-05
Volume
114
Issue
19
Pages
4064-4076
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2009-04-214916
Cited by
135
References
6
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review