Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein.
The liver is highly susceptible to a number of pathological insults, including ischemia/reperfusion injury. One of the striking consequences of liver injury is the associated pulmonary dysfunction that may be related to the release of hepatic-derived cytokines. We have previously employed an animal model of hepatic ischemia/reperfusion injury, and demonstrated that this injury causes the production and release of hepatic-derived TNF, which mediates a neutrophil-dependent pulmonary microvascular injury. In this study, we have extended these previous observations to assess whether an interrelationship between TNF and the neutrophil chemoattractant/activating factor, epithelial neutrophil activating protein-78 (ENA-78), exists that may be accountable for the pathology of lung injury found in this model. In the context of hepatic ischemia/reperfusion injury, we demonstrated the following alterations in lung pathophysiology: (a) an increase in pulmonary microvascular permeability, lung neutrophil sequestration, and production of pulmonary-derived ENA-78; (b) passive immunization with neutralizing TNF antiserum resulted in a significant suppression of pulmonary-derived ENA-78; and (c) passive immunization with neutralizing ENA-78 antiserum resulted in a significant attenuation of pulmonary neutrophil sequestration and microvascular permeability similar to our previous studies with anti-TNF. These findings support the notion that pulmonary ENA-78 produced in response to hepatic-derived TNF is an important mediator of lung injury.
Colletti
L M
LM
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor 48109-0360.
Kunkel
S L
SL
Walz
A
A
Burdick
M D
MD
Kunkel
R G
RG
Wilke
C A
CA
Strieter
R M
RM
D000818:Animals; D001483:Base Sequence; D002199:Capillary Permeability / Q000502:physiology; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D008099:Liver / Q000601:surgery*; D008168:Lung / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D016209:Interleukin-8; D012333:RNA, Messenger