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

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-alpha, IL-6, IL-10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1alpha, 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 alpha-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.

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@article{Frink2007KeratinocytederivedCP, title={Keratinocyte-derived chemokine plays a critical role in the induction of systemic inflammation and tissue damage after trauma-hemorrhage.}, author={Michael Frink and Ya-Ching Hsieh and Chi-Hsun Hsieh and H Chr Pape and Mashkoor A. Choudhry and Martin G. Schwacha and Irshad H. Chaudry}, journal={Shock}, year={2007}, volume={28 5}, pages={576-81} }