Enhanced pulmonary expression of CXC chemokines during hepatic ischemia/reperfusion-induced lung injury in mice.
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.
Yoshidome
H
H
Department of Surgery, University of Louisville, Louisville, Kentucky, 40292, USA.
Lentsch
A B
AB
Cheadle
W G
WG
Miller
F N
FN
Edwards
M J
MJ
D000818:Animals; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics*; D019743:Chemokines, CXC; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression; D018836:Inflammation Mediators; D008099:Liver / Q000098:blood supply*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000235:genetics; D009504:Neutrophils / Q000473:pathology; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D015846:Monokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C074302:keratinocyte-derived chemokines