Keratinocyte-derived chemokine plays a critical role in the induction of systemic inflammation and tissue damage after trauma-hemorrhage

Michael Frink, Ya Ching Hsieh, Chi Hsun Hsieh, Hans Christoph Pape, Mashkoor A. Choudhry, Martin G. Schwacha, Irshad H. Chaudry

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Neutrophil infiltration is a crucial step in the development of organ dysfunction after trauma. We have previously shown that keratinocyte-derived chemokine (KC), a chemoattractant for neutrophils, is up-regulated after trauma-hemorrhage. To determine the role of KC after trauma-hemorrhage, the effect of a KC-neutralizing antibody on the posttraumatic inflammatory response was examined. One hour before surgery, male C3H/HeN mice were treated with an anti-KC antibody or isotype control. Animals were subjected to sham operation or trauma-hemorrhage and resuscitated with Ringer lactate thereafter. They were killed 2 h later, and Kupffer cells were isolated. Plasma levels, Kupffer cell production, and lung and liver content of TNF-α, IL-6, IL-10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1α, and KC were determined by BD cytometric bead arrays. Myeloperoxidase content in lung and liver were measured as a parameter for neutrophil infiltration, and wet-to-dry weight ratios of these organs were also determined. Hepatocyte damage was assessed by measuring α-gluthathione S-transferase concentration. Administration of the anti-KC antibody before trauma-hemorrhage prevented increases in KC plasma levels, which was accompanied by amelioration of neutrophil infiltration and edema formation in lung and liver after trauma-hemorrhage. No effect on other cytokines in plasma or Kupffer cell release was observed. These results suggest that KC plays a pivotal role in neutrophil infiltration and organ damage after trauma-hemorrhage and resuscitation.

Original languageEnglish (US)
Pages (from-to)576-581
Number of pages6
JournalShock
Volume28
Issue number5
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Keywords

  • Cytokines
  • KC
  • Neutrophil infiltration
  • Organ damage

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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