Keratinocyte-derived chemokine plays a critical role in the induction of systemic inflammation and tissue damage after trauma-hemorrhage.
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.
Frink
Michael
M
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
Hsieh
Ya-Ching
YC
Hsieh
Chi-Hsun
CH
Pape
Hans-Christoph
HC
Choudhry
Mashkoor A
MA
Schwacha
Martin G
MG
Chaudry
Irshad H
IH
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D054360:Chemokine CXCL1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006470:Hemorrhage / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D012151:Resuscitation; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D014947:Wounds and Injuries / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D000906:Antibodies; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D009195:Peroxidase; D005982:Glutathione Transferase