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

Academic Article

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. ©2007The Shock Society.
  • Authors

    Published In

  • Shock  Journal
  • Digital Object Identifier (doi)

    Author List

  • Frink M; Hsieh YC; Hsieh CH; Pape HC; Choudhry MA; Schwacha MG; Chaudry IH
  • Start Page

  • 576
  • End Page

  • 581
  • Volume

  • 28
  • Issue

  • 5