Bone marrow stromal cells attenuate sepsis via prostaglandin E2—dependent reprogramming of host macrophages to increase their interleukin-10 production

By K. Nemeth, Asada Leelahavanichkul, P. S. Yuen, Balázs Mayer, Alissa Parmelee, Kent Doi, P. Robey, Kantima Leelahavanichkul, B. Koller, Jared M Brown and 4 more. Nature Medicine, 2008

2,301 citations recorded by the source corpus.

Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs—also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-α) reprogram macrophages by releasing prostaglandin E2 that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups.

Subfields: Genetics, Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/5e4b47726c78cef31093239c74328c76a921e8a4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Michael A. Matthay
2. R. Zemans
3. R. Lee
4. A. Caplan
5. Jaehyup Kim
6. P. Hematti
7. C. Gregory
8. Aline M. Betancourt

In Pulmonary and Respiratory Medicine

1. R. Zemans
2. Michael A. Matthay
3. N. Gupta
4. V. Serikov
5. A. Caplan
6. W. Fibbe
7. Maria Ester Bernardo

In Surgery

1. R. Lee
2. A. Caplan
3. Jaehyup Kim
4. P. Hematti
5. C. Gregory
6. Michael A. Matthay
7. S. Goodman
8. Jeffrey L Spees

Citations in the corpus

• Antibacterial Effect of Human Mesenchymal Stem Cells Is Mediated in Part from Secretion of the Antimicrobial Peptide LL-37 (2010, background): “5A–5D), reflecting the immunomodulatory properties of MSCs [18–22].”
• Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages (2009, background): “7 cells activated by silica or LPS to secrete TNF-α [57], and Nemeth et al. investigated the effect of mouse BM-derived MSCs in a murine model of septicemia and showed LPS stimulated macrophages produced more IL-10 when co-cultured with BM-derived MSCs [58].”
• The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes (2018, background): “M2b macrophages, which express CD86, CD68, and MHCII, are stimulated by immune complexes and TLF/Il-1 agonists (Ogle et al., 2016; Hesketh et al., 2017).”
• The Acute Respiratory Distress Syndrome: Pathogenesis and Treatment (2011, background): “Analogously, the presence of anti-inflammatory cytokines such as IL-10 may play an important role in the resolution of lung inflammation (68).”