PMID- 34636179
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20211214
IS  - 2050-4527 (Electronic)
IS  - 2050-4527 (Linking)
VI  - 9
IP  - 4
DP  - 2021 Dec
TI  - Immunomodulation of endothelial cells induced by macrolide therapy in a model of 
      septic stimulation.
PG  - 1656-1669
LID - 10.1002/iid3.518 [doi]
AB  - OBJECTIVES: Sepsis is defined as the host's inflammatory response to a 
      life-threatening infection. The endothelium is implicated in immunoregulation 
      during sepsis. Macrolides have been proposed to display immunomodulatory 
      properties. The goal of this study was to analyze whether macrolides can exert 
      immunomodulation of endothelial cells (ECs) in an experimental model of sepsis. 
      METHODS: Human ECs were stimulated by proinflammatory cytokines and 
      lipopolysaccharide before exposure to macrolides. ECs phenotypes were analyzed by 
      flow cytometry. Cocultures of ECs and peripheral blood mononuclear cells (PBMCs) 
      were performed to study the ECs ability to alter T-cell viability and 
      differentiation in the presence of macrolides. Soluble factor production was 
      assessed. RESULTS: ECs act as non-professional antigen presenting cells and 
      expressed human leukocyte antigen (HLA) antigens, the adhesion molecules CD54, 
      CD106, and the coinhibitory molecule CD274 after septic stimulation. Incubation 
      with macrolides induced a significant decrease of HLA class I and HLA class II 
      HLA-DR on septic-stimulated ECs, but did not alter either CD54, CD106, nor CD274 
      expression. Interleukin-6 (IL-6) and IL-8 production by stimulated ECs were 
      unaltered by incubation with macrolides, whereas Clarithromycin exposure 
      significantly decreased IL-6 gene expression. In cocultures of septic ECs with 
      PBMCs, neither the proportion of CD4 (+ ) , CD8 (+ ) T nor their viability was 
      altered by macrolides. T-helper lymphocyte subsets Th1, Th17, and Treg 
      polarization by stimulated ECs were unaltered by macrolides. CONCLUSION: This 
      study reports phenotypic and gene expression changes in septic-stimulated ECs 
      exposed to macrolides, without resulting in altered immunogenicity of ECs in 
      co-cultures with PBMCs. In vivo studies may help to further understand the impact 
      of macrolide therapy on ECs immune homeostasis during sepsis.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Pons, Stephanie
AU  - Pons S
AUID- ORCID: 0000-0002-7372-3563
AD  - Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Universite 
      de Paris, Paris, France.
AD  - Department of Anesthesiology and Critical Care, Pitie-Salpetriere Hospital, GRC 
      29, AP-HP, DMU DREAM, Sorbonne University, Paris, France.
FAU - Arrii, Eden
AU  - Arrii E
AD  - Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Universite 
      de Paris, Paris, France.
FAU - Arnaud, Marine
AU  - Arnaud M
AD  - Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Universite 
      de Paris, Paris, France.
FAU - Loiselle, Maud
AU  - Loiselle M
AD  - Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Universite 
      de Paris, Paris, France.
FAU - Ferry, Juliette
AU  - Ferry J
AD  - Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Universite 
      de Paris, Paris, France.
FAU - Nouacer, Manel
AU  - Nouacer M
AD  - Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Universite 
      de Paris, Paris, France.
FAU - Lion, Julien
AU  - Lion J
AD  - Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Universite 
      de Paris, Paris, France.
FAU - Cohen, Shannon
AU  - Cohen S
AD  - Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Universite 
      de Paris, Paris, France.
FAU - Mooney, Nuala
AU  - Mooney N
AD  - Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Universite 
      de Paris, Paris, France.
FAU - Zafrani, Lara
AU  - Zafrani L
AD  - Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Universite 
      de Paris, Paris, France.
AD  - Medical Intensive Care Unit, AP-HP, Saint-Louis Teaching Hospital, Paris, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211012
PL  - England
TA  - Immun Inflamm Dis
JT  - Immunity, inflammation and disease
JID - 101635460
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Macrolides)
SB  - IM
MH  - Endothelial Cells
MH  - *HLA-DR Antigens
MH  - Humans
MH  - Immunomodulation
MH  - Leukocytes, Mononuclear
MH  - *Macrolides/pharmacology
PMC - PMC8589380
OTO - NOTNLM
OT  - antibiotics
OT  - endothelium
OT  - immunoregulation
OT  - inflammation
OT  - septic shock
COIS- The authors declare that there is no conflict of interest.
EDAT- 2021/10/13 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/10/12
CRDT- 2021/10/12 07:03
PHST- 2021/08/15 00:00 [revised]
PHST- 2021/06/28 00:00 [received]
PHST- 2021/08/17 00:00 [accepted]
PHST- 2021/10/13 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/10/12 07:03 [entrez]
PHST- 2021/10/12 00:00 [pmc-release]
AID - IID3518 [pii]
AID - 10.1002/iid3.518 [doi]
PST - ppublish
SO  - Immun Inflamm Dis. 2021 Dec;9(4):1656-1669. doi: 10.1002/iid3.518. Epub 2021 Oct 
      12.