Attenuation of leukocyte adhesion by recombinant TNF-binding protein after hemorrhagic shock in the rat.
Ischemia/reperfusion injury involves a large number of humoral and cellular mediators that activate leukocytes that subsequently migrate to local tissues. Tumor necrosis factor (TNF)-alpha may be one of the most important mediators of this post-shock inflammatory response. In this study, we investigated the influence of a recombinant Type I (55 kDa) TNF-binding protein (TNF-BP) on leukocyte-endothelial interactions in the liver after hemorrhagic shock. Hemorrhagic shock was induced in female Sprague-Dawley rats (40 mmHg for 90 min) and a standardized resuscitation regimen was applied. At the time of resuscitation, animals were treated intravenously with either TNF-BP 4 mg/kg or placebo. The liver microcirculation was investigated using intravital fluorescence microscopy and immunohistochemistry at 5 h and 48 h after reperfusion. At 5 h, treatment with TNF-BP significantly reduced temporary leukocyte adhesion in the liver sinusoids as well as mean adhesion time of leukocytes in the hepatic central vein. In contrast, after 48 h, permanent leukocyte adhesion in the central hepatic vein was significantly reduced in the group receiving TNF-BP, whereas temporary leukocyte adhesion and mean adhesion time did not differ between the two groups. Both types of leukocyte adhesion, rolling adhesion after 5 h and firm adhesion after 48 h, were reduced in the group treated with TNF-BP, thereby suggesting a long-lasting anti-inflammatory effect.
Department of Trauma Surgery, Johann Wolfgang Goethe-University, 60590 Frankfurt, Germany.
Marcus
M
Maier
Hubert
H
Ströbele
Jaqueline
J
Voges
Clemens
C
Bauer
Ingo
I
Marzi
D000818:Animals; D002352:Carrier Proteins / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006400:Hematocrit; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000627:therapeutic use; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000276:immunology / Q000473:pathology; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha
D002352:Carrier Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C069521:recombinant human tumor necrosis factor-binding protein-1