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Molecular Medicine

, Volume 14, Issue 5–6, pp 238–246 | Cite as

Gram-Positive and Gram-Negative Bacteria Synergize with Oxidants to Release CXCL8 from Innate Immune Cells

  • Mark J. Paul-Clark
  • Rosalinda Sorrentino
  • Lucy K. Bailey
  • Shiranee Sriskandan
  • Jane A. Mitchell
Research Article

Abstract

We have recently demonstrated that oxidants can activate monocytes via an action on Toll-like receptor (TLR) 2; however, it is unclear what functional consequence this has on immune surveillance for Gram-negative and -positive bacteria. Gram-negative and -positive bacteria and their related pathogen-associated molecular patterns (PAMPs) are sensed by TLR4 and TLR2, respectively. In the current study, we used a human monocyte cell line to show that oxidants prime cells to subsequent challenge with Gram-negative or -positive bacteria as well as PAMPs specific for TLR4 (LPS), TLR2/1 (Pam3CSK4), TLR2/6 (FSL-1), Nod1 (FK565), and Nod2 (MDP Lys 18). Similarly, activation of TLR4 with LPS primed for subsequent activation of cells by agonists of the TLR2/6 or TLR2/1 complex. However, no synergy was noted when cells were costimulated with Pam3CSK4 and FSL-1. We then tested blood (and isolated monocytes) derived from healthy smokers, which is oxidant primed, making it more sensitive to bacterial or PAMP stimulation when compared with blood of nonsmokers. Thus an oxidant stimulation, possibly via an action on TLR2 or associated transduction pathways, provides a signal that initiates inflammatory responses and sensitizes cells to pathogenic insults.

Notes

Acknowledgments

M.J.P.C. was supported by The British Lung Foundation; this work was also funded by the British Heart Foundation and the Wellcome Trust.

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Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  • Mark J. Paul-Clark
    • 1
  • Rosalinda Sorrentino
    • 1
  • Lucy K. Bailey
    • 1
  • Shiranee Sriskandan
    • 2
  • Jane A. Mitchell
    • 1
  1. 1.Cardiothoracic Pharmacology, Unit of Critical Care medicine, National Heart and Lung InstituteImperial College LondonLondonUK
  2. 2.Department of Infectious DiseasesImperial College Faculty of MedicineLondonUK

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