Downregulation of Blood Monocyte HLA-DR in ICU Patients Is Also Present in Bone Marrow Cells

PLoS One. 2016 Nov 28;11(11):e0164489. doi: 10.1371/journal.pone.0164489. eCollection 2016.

Abstract

Background: The downregulation of blood monocyte HLA-DR expression also occurs in tissue infiltrative cells in a context of acute clinical inflammation, especially sepsis. This context favors the development of secondary infections and results from various mechanisms. Little is known about HLA-DR expression on bone marrow (BM) cells of the monocyte lineage, the source of circulating monocytes. This study analyzed the BM HLA-DR expression in ICU patients compared to BM monocytes from non-ICU patients and to blood monocytes of control healthy donors. A potential dysfunction of myeloid differentiation was investigated in a sub-population of these ICU patients to characterize the phenotype of the immature forms of monocytes and granulocytes in BM.

Methods and findings: BM and blood were drawn from 33 ICU and 9 non-ICU patients having a BM analysis to precise the etiology of abnormal low count in blood cells. The data were compared with blood cells of 28 control donors. Flow cytometry was used for both HLA-DR expression and phenotyping of immature forms of monocytes and granulocytes. HLA-DR expression was downregulated in both blood and BM monocyte in ICU patients compared to BM of non-ICU patients and blood of control donors. Amplitude of HLA-DR downregulation was comparable in septic and non-septic ICU patients. The phenotype of immature forms of monocytes and granulocytes in BM (n = 11) did not show abnormal myeloid (monocyte + granulocyte) differentiation.

Conclusion: The downregulation of HLA-DR in BM monocyte lineage is present in ICU patients without major changes in myeloid cells. It may result from a regulation mediated by soluble and/or neuro-endocrine factors present in BM cell microenvironment.

MeSH terms

  • Aged
  • Bone Marrow Cells / metabolism*
  • CD11b Antigen / blood
  • CD11b Antigen / metabolism
  • Case-Control Studies
  • Down-Regulation
  • Female
  • GPI-Linked Proteins / blood
  • GPI-Linked Proteins / metabolism
  • HLA-DR Antigens / blood
  • HLA-DR Antigens / metabolism*
  • Humans
  • Intensive Care Units
  • L-Selectin / blood
  • L-Selectin / metabolism
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Monocytes / pathology
  • Prospective Studies
  • Receptors, CCR2 / blood
  • Receptors, CCR2 / metabolism
  • Receptors, IgG / blood
  • Receptors, IgG / metabolism
  • Shock, Septic / blood
  • Shock, Septic / metabolism
  • Thrombocytopenia / blood
  • Thrombocytopenia / metabolism

Substances

  • CCR2 protein, human
  • CD11b Antigen
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • HLA-DR Antigens
  • ITGAM protein, human
  • Receptors, CCR2
  • Receptors, IgG
  • L-Selectin

Grants and funding

This work was supported by a grant from the University Paris Diderot, Sorbonne Paris Cité grant from INSERM U 1160 for material, products 2015-2017; and partially from an Eli Lilly Grant for RCT in sepsis Trial PROWESS Shock. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.