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 language | English (US) |
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Pages (from-to) | 710-718 |
Number of pages | 9 |
Journal | Journal of Leukocyte Biology |
Volume | 62 |
Issue number | 6 |
DOIs | |
State | Published - Dec 1997 |
Externally published | Yes |
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