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Immunomodulatory action of G‐CSF In a rat model of endotoxin‐induced liver injury: an intravital microscopic analysis of Kupffer cell and leukocyte response
Author(s) -
Vollmar Brigitte,
Messner Sven,
Wanner Guido A.,
Hartung Thomas,
Menger Michael D.
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.62.6.710
Subject(s) - intravital microscopy , kupffer cell , tumor necrosis factor alpha , lipopolysaccharide , biology , inflammation , proinflammatory cytokine , cytokine , immune system , in vivo , pathology , immunology , medicine , microbiology and biotechnology
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 dys function. 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. J. Leukoc. Biol 62: 710–718; 1997.