Enhanced pulmonary expression of CXC chemokines during hepatic ischemia/reperfusion-induced lung injury in mice

J Surg Res. 1999 Jan;81(1):33-7. doi: 10.1006/jsre.1998.5490.


Background: Hepatic ischemia/reperfusion injury during both hepatic resection and transplantation may lead to local and systemic organ dysfunction. Proinflammatory mediators released by Kupffer cells during the initial phase of ischemia/reperfusion are thought to be involved in the development of neutrophil-mediated lung injury. However, the precise factors involved in lung recruitment of neutrophils are unclear. The objective of current study was to determine whether the CXC chemokines, macrophage inflammatory protein-2 (MIP-2) and KC, contribute to pulmonary neutrophil recruitment and injury following hepatic ischemia/reperfusion.

Methods: C57BL/6 mice were subjected to 90 min of partial hepatic ischemia and 3, 6, and 9 h of reperfusion. Neutrophil accumulation in lung was assessed by lung content of myeloperoxidase (MPO). MIP-2 and KC mRNA were measured using RT-PCR. Lung edema was quantified by wet to dry weight ratios.

Results: Three hours after hepatic reperfusion, serum levels of tumor necrosis factor-alpha were increased. Lung expression of both MIP-2 and KC mRNA was also increased at this time. Both MIP-2 and KC mRNA expression remained elevated 9 h after reperfusion, although levels of MIP-2 mRNA were significantly lower than at 3 h. Pulmonary recruitment of neutrophils was increased within 3 h after reperfusion, but returned to baseline levels by 9 h. Lung edema was increased 3 and 9 h after reperfusion. Neutralization of MIP-2 or KC with antibody significantly decreased lung edema 9 h after reperfusion.

Conclusions: These data suggest that mediators released during hepatic ischemia/reperfusion induce the expression of MIP-2 and KC in the lung. In addition, it appears that MIP-2 and KC contribute to lung neutrophil accumulation and the associated pulmonary injury following hepatic ischemia/reperfusion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines / genetics*
  • Chemokines, CXC
  • Cytokines / genetics
  • Gene Expression
  • Inflammation Mediators
  • Liver / blood supply*
  • Lung / metabolism*
  • Lung / pathology
  • Lung Diseases / etiology
  • Lung Diseases / metabolism*
  • Lung Diseases / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monokines / genetics
  • Neutrophils / pathology
  • Pulmonary Edema / etiology
  • Pulmonary Edema / metabolism
  • Pulmonary Edema / pathology
  • RNA, Messenger / metabolism
  • Reperfusion Injury / complications*
  • Tumor Necrosis Factor-alpha / metabolism


  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines
  • Chemokines, CXC
  • Cxcl1 protein, mouse
  • Cytokines
  • Inflammation Mediators
  • Monokines
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • keratinocyte-derived chemokines