Immunomodulatory action of G-CSF in a rat model of endotoxin-induced liver injury: An intravital microscopic analysis of Kupffer cell and leukocyte response

Brigitte Vollmar, Sven Messner, Guido A. Wanner, Thomas Hartung, Michael D. Menger

Research output: Contribution to journalArticlepeer-review

Abstract

In contrast to the anticipation that in sepsis granulocyte colony- stimulating factor (G-CSF) would overactivate the nonspecific immune system by recruiting and priming leukocytes with consequent aggravation of inflammatory tissue lesions, recombinant (r) G-CSF pretreatment was protective in various experimental non-neutropenic models of inflammation. The mechanisms of protection, however, are not fully understood. Using intravital fluorescence microscopy, we show that rG-CSF enhances leukocyte endothelial cell interaction within the microvasculature of normal rat livers, whereas rG-CSF pretreatment of animals exposed to lipopolysaccharide (LPS) attenuates the LPS-induced leukocytic response, including stasis in sinusoids as well as rolling and adherence in postsinusoidal venules with subsequent tissue infiltration. Moreover, rG-CSF, which did not affect Kupffer cell activity in normal rat livers, reduced the immediate activation of Kupffer cells on LPS exposure, as indicated in vivo by the delayed adherence/phagocytosis of intra-arterially administered latex particles associated with attenuation of proinflammatory cytokine release (tumor necrosis factor α and interleukin-6). Finally, rG-CSF reduced LPS-induced nutritive perfusion failure and hepatocellular excretory dysfunction. This study provides evidence for a distinct, possibly tumor necrosis factor α- dependent modulation of LPS-induced cellular response within the liver by rG- CSF, thereby achieving protection against microcirculatory perfusion failure and hepatic dysfunction.

Original languageEnglish (US)
Pages (from-to)710-718
Number of pages9
JournalJournal of Leukocyte Biology
Volume62
Issue number6
DOIs
StatePublished - Dec 1997
Externally publishedYes

Keywords

  • Hepatic microcirculation
  • Kupffer cell activity
  • Leukocyte endothelial cell interaction
  • Septic organ failure
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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