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Increased MerTK expression in circulating innate immune cells of patients with septic shock

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Abstract

Purpose

A new pathway of three protein tyrosine kinase receptors, namely, the TAM receptor family [Tyro-3, Axl and Mer tyrosine kinase (MerTK)], has recently been described to negatively control immune responses. The objective of this prospective, observational, clinical study was to investigate the expression patterns of TAM receptors in circulating white blood cells collected from patients with septic shock.

Methods

The expression of TAM receptors was measured by flow cytometry in circulating leukocytes from patients with septic shock sampled on days (D) 1–2 (n = 47) and D3–4 (n = 37) after the onset of shock, severe trauma patients at D1–2 after trauma (n = 51) and healthy individuals (n = 23).

Results

On D1–2 after injury, MerTK was overexpressed in monocytes and neutrophils collected from patients with septic shock in comparison with those collected from healthy volunteers and trauma patients. This phenomenon was also observed for mRNA. Conversely, the expression of Tyro-3 and Axl was higher in monocytes from trauma patients versus healthy volunteers or those in septic shock. MerTK expression between D1–2 and D3–4 remained elevated in patients suffering from septic shock who died or developed an intensive care unit-acquired infection, whereas it decreased in patients who recovered uneventfully. This in vivo observed expression pattern was reproduced ex vivo after the incubation of healthy volunteer cells with plasma from septic shock or trauma patients.

Conclusions

MerTK expression in circulating innate immune cells is increased in patients with septic shock in comparison with healthy volunteers and trauma patients. Persistent MerTK overexpression after septic shock is associated with adverse outcome. The role of this family of receptors in the pathophysiology of injury-induced immune dysfunctions deserves to be specifically investigated.

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Acknowledgments

The authors would like to thank H. Vallin, M. Provent, N. Panel and C. Jouvene-Faure from Lyon-Sud and HEH ICUs (Hospices Civils de Lyon) for collecting patients’ inclusion and clinical data gathering as well as Anne Portier (Hospices Civils de Lyon, Immunology Lab, E. Herriot hospital) for her technical assistance. This work was supported by funds from the Hospices Civils de Lyon (GM).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Laboratoire d’Immunologie, Hôpital E. Herriot, Hospices Civils de Lyon, 5 place d’Arsonval, 69437, Lyon cedex 03, France

    Caroline Guignant, Fabienne Venet, Julie Demaret & Guillaume Monneret

  2. Hospices Civils de Lyon, Université Claude Bernard Lyon I, EAM 4174, Lyon, France

    Caroline Guignant, Fabienne Venet, Julie Demaret, Arnaud Friggeri, Bernard Allaouchiche, Alain Lepape & Guillaume Monneret

  3. Laboratoire d’Hémostase, Hôpital E. Herriot, Hospices Civils de Lyon, Lyon, France

    Christophe Nougier

  4. Laboratoire Commun de Recherche HCL–Biomérieux, Hôpital E. Herriot, Lyon, France

    Séverine Planel

  5. Service de Réanimation, Hôpital E. Herriot, Hospices Civils de Lyon , Lyon, France

    Aurélie Gouel-Chéron & Bernard Allaouchiche

  6. Intensive Care Units, CH Lyon-Sud, Hospices Civils de Lyon, Lyon, France

    Arnaud Friggeri & Alain Lepape

Authors
  1. Caroline Guignant
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  2. Fabienne Venet
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  3. Séverine Planel
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  4. Julie Demaret
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  5. Aurélie Gouel-Chéron
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  7. Arnaud Friggeri
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  8. Bernard Allaouchiche
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  9. Alain Lepape
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  10. Guillaume Monneret
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Corresponding author

Correspondence to Guillaume Monneret.

Additional information

C. Guignant and F. Venet contributed equally to this work.

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Guignant, C., Venet, F., Planel, S. et al. Increased MerTK expression in circulating innate immune cells of patients with septic shock. Intensive Care Med 39, 1556–1564 (2013). https://doi.org/10.1007/s00134-013-3006-9

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  • DOI: https://doi.org/10.1007/s00134-013-3006-9

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