Potential role of hepatic macrophages in neutrophil-mediated liver injury in rats with sepsis

Abstract

We investigated the pathogenesis of septic liver injury in rats caused by cecal ligation and puncture. In this model, numerous neutrophils accumulated in the liver in parallel with the development of liver dysfunction. The supernatants of hepatic macrophages isolated from these septic rats 24 hr after cecal ligation and puncture had enhanced chemotactic activities for human neutrophils. These results suggest that in sepsis, hepatic macrophages attract neutrophils to the liver. Human neutrophils preincubated in this macrophage supernatant had the following biological activities not seen in the sham-operated controls. (a) They became more adherent to cultured endothelial cells through up-regulation of adhesion molecules such as CD11b/CD18, (b) their chemiluminescence was markedly elevated. These functional changes of cecal ligation and puncture hepatic macrophages were the same as those in endotoxin-pretreated hepatic macrophages after isolation from normal rats. Therefore we suspect that hepatic macrophages are activated by portal vein endotoxin in sepsis. These activated hepatic macrophages secreted chemical mediators of inflammation, including leukotriene B4 and tumor necrosis factor. In conclusion, hepatic macrophages seem to interact closely with neutrophils and play an important role in the pathogenesis of septic liver injury.

The Epidemiology of Sepsis in General Surgery Patients

“…Potential causes include secondary dysfunction related to crosstalk with other failing organs, 32 ongoing damage to hepatocytes by inflammatory mediators, 35 and microvascular thrombosis of the liver sinusoids secondary to ongoing inflammation. 36 Patients with severe sepsis and septic shock had fewer ventilator-free days and fewer ICU-free days than those with sepsis (p Ͼ 0.001). In addition, patients with severe sepsis and septic shock were less likely to be discharged directly home.…”

Advances in sepsis-associated liver dysfunction

“…During the process of septic response, activated KCs release leukotriene B4 and TNF-α, which in turn attract blood neutrophils into the liver and activate them. [16] Apoptotic hepatocytes have also been shown to function as chemotactic signals, triggering neutrophil transmigration. [17] Upregulation of endothelial integrins and intercellular adhesion molecule (ICAM)-1 also promotes neutrophil migration in LPS-induced liver injury.…”

Induction of endotoxin tolerance in transgenic mouse liver expressing creatine kinase

“…9 Kupffer cell activation appears to play a kine response, resulting in endotoxin tolerance. To study the effects of phosphocretors.…”

“…9 Kupffer cell activation appears to play a kine response, resulting in endotoxin tolerance. 9 Kupffer cell activation appears to play a kine response, resulting in endotoxin tolerance.…”