Lipopolysaccharide desensitizes monocytes-macrophages to CD40 ligand stimulation

Anna Sinistro, Chiara Ciaprini, Silvia Natoli, Emanuele Sussarello, F. C. Carducci, Cristiana Almerighi, Marcella Capozzi, Francesca Bolacchi, Giovanni Rocchi, Alberto Bergamini

Research output: Contribution to journalArticle

Abstract

Polymicrobial sepsis induces the suppression of macrophage function as determined by a reduction of pro-inflammatory cytokine production upon re-exposure to lipopolysaccharide (LPS) in vitro. Here, we examined whether macrophages were refractory to only LPS or if they were unable to respond to other stimuli such as CD40 ligand (CD40L). Monocytic cells exposed in vitro to LPS showed a dose-dependent reduction of their ability to produce interleukin-12 and tumour necrosis factor-α upon subsequent CD40L stimulation, as compared to cells stimulated with CD40L alone. Similarly, LPS interfered with the up-regulation of CD40, CD80 and CD86 induced by CD40L in monocytic cells. The effect of LPS on the response of monocytes to CD40L was similar whether these cells were directly exposed to LPS or cocultured with LPS-pretreated cells, indicating that soluble factors released by LPS stimulation could mediate tolerance to CD40L. We also show that the functional alterations induced by LPS in monocytes can be reversed by indomethacin, thus suggesting a role for inducible cyclooxygenase in mediating the LPS-induced hyporesponsive state of monocytes to CD40L. In conclusion, we propose that in vitro CD40L tolerance may be an appropriate model of monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.

Original languageEnglish
Pages (from-to)362-370
Number of pages9
JournalImmunology
Volume122
Issue number3
DOIs
Publication statusPublished - Nov 2007

Fingerprint

CD40 Ligand
Lipopolysaccharides
Monocytes
Macrophages
Interleukin-12
Prostaglandin-Endoperoxide Synthases
Indomethacin
Immunosuppression
Sepsis
Up-Regulation
Tumor Necrosis Factor-alpha
Cytokines

Keywords

  • CD40 ligand
  • Lipopolysaccharide
  • Macrophages
  • Sepsis

ASJC Scopus subject areas

  • Immunology

Cite this

Sinistro, A., Ciaprini, C., Natoli, S., Sussarello, E., Carducci, F. C., Almerighi, C., ... Bergamini, A. (2007). Lipopolysaccharide desensitizes monocytes-macrophages to CD40 ligand stimulation. Immunology, 122(3), 362-370. https://doi.org/10.1111/j.1365-2567.2007.02648.x

Lipopolysaccharide desensitizes monocytes-macrophages to CD40 ligand stimulation. / Sinistro, Anna; Ciaprini, Chiara; Natoli, Silvia; Sussarello, Emanuele; Carducci, F. C.; Almerighi, Cristiana; Capozzi, Marcella; Bolacchi, Francesca; Rocchi, Giovanni; Bergamini, Alberto.

In: Immunology, Vol. 122, No. 3, 11.2007, p. 362-370.

Research output: Contribution to journalArticle

Sinistro, A, Ciaprini, C, Natoli, S, Sussarello, E, Carducci, FC, Almerighi, C, Capozzi, M, Bolacchi, F, Rocchi, G & Bergamini, A 2007, 'Lipopolysaccharide desensitizes monocytes-macrophages to CD40 ligand stimulation', Immunology, vol. 122, no. 3, pp. 362-370. https://doi.org/10.1111/j.1365-2567.2007.02648.x
Sinistro, Anna ; Ciaprini, Chiara ; Natoli, Silvia ; Sussarello, Emanuele ; Carducci, F. C. ; Almerighi, Cristiana ; Capozzi, Marcella ; Bolacchi, Francesca ; Rocchi, Giovanni ; Bergamini, Alberto. / Lipopolysaccharide desensitizes monocytes-macrophages to CD40 ligand stimulation. In: Immunology. 2007 ; Vol. 122, No. 3. pp. 362-370.
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