Murine Myeloid Progenitors Attenuate Immune Dysfunction Induced by Hemorrhagic Shock

Stem Cell Reports. 2021 Feb 9;16(2):324-336. doi: 10.1016/j.stemcr.2020.12.014. Epub 2021 Jan 21.


Hemorrhagic shock induces an aberrant immune response characterized by simultaneous induction of a proinflammatory state and impaired host defenses. The objective of this study was to evaluate the impact of conditionally immortalized neutrophil progenitors (NPs) on this aberrant immune response. We employed a mouse model of hemorrhagic shock, followed by the adoptive transfer of NPs and subsequent inoculation of Staphylococcus aureus to induce pneumonia. We observed that transplant of NPs decreases the proportion of host neutrophils that express programmed death ligand 1 and intercellular adhesion molecule 1 in the context of prior hemorrhage. Following hemorrhage, NP transplant decreased proinflammatory cytokines in the lungs, increased neutrophil migration into the airspaces, and enhanced bacterial clearance. Further, hemorrhagic shock improved NP engraftment in the bone marrow. These results suggest that NPs hold the potential for use as a cellular therapy in the treatment and prevention of secondary infection following hemorrhagic shock.

Keywords: ICAM-1; PD-L1; Staphylococcus aureus; bone marrow engraftment; cell therapy; hemorrhagic shock; myeloid progenitors; neutrophil priming; pneumonia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B7-H1 Antigen / metabolism
  • Bone Marrow / immunology
  • Cell Line
  • Cell Movement
  • Cell- and Tissue-Based Therapy
  • Cytokines / metabolism
  • Disease Models, Animal
  • Immunity
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lung / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Progenitor Cells / immunology*
  • Myeloid Progenitor Cells / metabolism*
  • Neutrophils / immunology*
  • Neutrophils / transplantation
  • Pneumonia / immunology*
  • Pneumonia / microbiology
  • Shock, Hemorrhagic / complications
  • Shock, Hemorrhagic / immunology*
  • Shock, Hemorrhagic / metabolism*
  • Staphylococcus aureus / immunology*


  • B7-H1 Antigen
  • Cytokines
  • Intercellular Adhesion Molecule-1