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Extracellular Histones Induce Chemokine Production in Whole Blood Ex Vivo and Leukocyte Recruitment In Vivo.

Westman, Johannes LU ; Papareddy, Praveen LU ; Dahlgren, Madelene LU ; Chakrakodi, Bhavya; Norrby-Teglund, Anna; Smeds, Emanuel LU ; Linder, Adam LU ; Mörgelin, Matthias LU ; Johansson Lindbom, Bengt LU and Egesten, Arne LU , et al. (2015) In PLoS Pathogens 11(12).
Abstract
The innate immune system relies to a great deal on the interaction of pattern recognition receptors with pathogen- or damage-associated molecular pattern molecules. Extracellular histones belong to the latter group and their release has been described to contribute to the induction of systemic inflammatory reactions. However, little is known about their functions in the early immune response to an invading pathogen. Here we show that extracellular histones specifically target monocytes in human blood and this evokes the mobilization of the chemotactic chemokines CXCL9 and CXCL10 from these cells. The chemokine induction involves the toll-like receptor 4/myeloid differentiation factor 2 complex on monocytes, and is under the control of... (More)
The innate immune system relies to a great deal on the interaction of pattern recognition receptors with pathogen- or damage-associated molecular pattern molecules. Extracellular histones belong to the latter group and their release has been described to contribute to the induction of systemic inflammatory reactions. However, little is known about their functions in the early immune response to an invading pathogen. Here we show that extracellular histones specifically target monocytes in human blood and this evokes the mobilization of the chemotactic chemokines CXCL9 and CXCL10 from these cells. The chemokine induction involves the toll-like receptor 4/myeloid differentiation factor 2 complex on monocytes, and is under the control of interferon-γ. Consequently, subcutaneous challenge with extracellular histones results in elevated levels of CXCL10 in a murine air pouch model and an influx of leukocytes to the site of injection in a TLR4 dependent manner. When analyzing tissue biopsies from patients with necrotizing fasciitis caused by Streptococcus pyogenes, extracellular histone H4 and CXCL10 are immunostained in necrotic, but not healthy tissue. Collectively, these results show for the first time that extracellular histones have an important function as chemoattractants as their local release triggers the recruitment of immune cells to the site of infection. (Less)
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PLoS Pathogens
volume
11
issue
12
publisher
Public Library of Science
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  • pmid:26646682
  • wos:000368332800038
  • scopus:84953327772
ISSN
1553-7366
DOI
10.1371/journal.ppat.1005319
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English
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6913a6db-b54e-439d-bc15-f3bab877dd79 (old id 8505375)
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http://www.ncbi.nlm.nih.gov/pubmed/26646682?dopt=Abstract
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2016-01-05 14:07:55
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@article{6913a6db-b54e-439d-bc15-f3bab877dd79,
  abstract     = {The innate immune system relies to a great deal on the interaction of pattern recognition receptors with pathogen- or damage-associated molecular pattern molecules. Extracellular histones belong to the latter group and their release has been described to contribute to the induction of systemic inflammatory reactions. However, little is known about their functions in the early immune response to an invading pathogen. Here we show that extracellular histones specifically target monocytes in human blood and this evokes the mobilization of the chemotactic chemokines CXCL9 and CXCL10 from these cells. The chemokine induction involves the toll-like receptor 4/myeloid differentiation factor 2 complex on monocytes, and is under the control of interferon-γ. Consequently, subcutaneous challenge with extracellular histones results in elevated levels of CXCL10 in a murine air pouch model and an influx of leukocytes to the site of injection in a TLR4 dependent manner. When analyzing tissue biopsies from patients with necrotizing fasciitis caused by Streptococcus pyogenes, extracellular histone H4 and CXCL10 are immunostained in necrotic, but not healthy tissue. Collectively, these results show for the first time that extracellular histones have an important function as chemoattractants as their local release triggers the recruitment of immune cells to the site of infection.},
  articleno    = {e1005319},
  author       = {Westman, Johannes and Papareddy, Praveen and Dahlgren, Madelene and Chakrakodi, Bhavya and Norrby-Teglund, Anna and Smeds, Emanuel and Linder, Adam and Mörgelin, Matthias and Johansson Lindbom, Bengt and Egesten, Arne and Herwald, Heiko},
  issn         = {1553-7366},
  language     = {eng},
  number       = {12},
  publisher    = {Public Library of Science},
  series       = {PLoS Pathogens},
  title        = {Extracellular Histones Induce Chemokine Production in Whole Blood Ex Vivo and Leukocyte Recruitment In Vivo.},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1005319},
  volume       = {11},
  year         = {2015},
}