Gadolinium chloride alters the acinar distribution of phagocytosis and balance between pro- and anti-inflammatory cytokines.
Gadolinium chloride (GdCl3) is commonly used to deplete the liver of Kupffer cells (KC) and has been shown to decrease hepatic phagocytic activity and to abolish hepatic expression of certain KC-specific antigens. However, the exact fate of the KCs after GdCl3 treatment remains unclear. To determine if GdCl3 actually decreases the total number of KCs in the liver, we labeled phagocytically-active KC by administering fluorescent-labeled latex beads to rats treated with either normal saline or GdCl3. Total hepatic fluorescence and the distribution of fluorescence within liver acini were evaluated by intravital microscopy. Hepatic mRNA levels of KCR, a KC-specific gene product, and Pu-1, a ubiquitous monocyte gene product, were assessed by Northern blot analysis, and differences in the expression of pro-inflammatory (tumor necrosis factor (TNF)-alpha) and anti-inflammatory (interleukin (IL)-10) cytokines were assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). Our results indicate that GdCl3 does not significantly reduce the number of phagocytically active cells in the liver, but alters the acinar distribution of these cells and may provoke a switch in the KC phenotype such that these cells no longer express KCR or IL-10. GdCl3 pretreatment inhibited stress-related induction of IL-10, but failed to down-regulate expression of TNF-alpha. This phenotypic change is likely to have important consequences because it permits relative overexpression of TNF-alpha.
Department of Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA.
R M
RM
Rai
J X
JX
Zhang
M G
MG
Clemens
A M
AM
Diehl
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000954:Antigens, Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D005456:Fluorescent Dyes; D005682:Gadolinium / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D007840:Latex; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008853:Microscopy / Q000379:methods; D010587:Phagocytosis / Q000187:drug effects*; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects; D000099232:Proto-Oncogene Protein Spi-1
D000893:Anti-Inflammatory Agents; D000954:Antigens, Surface; D016207:Cytokines; D005456:Fluorescent Dyes; D005682:Gadolinium; D016753:Interleukin-10; D007840:Latex; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D000099232:Proto-Oncogene Protein Spi-1; C038958:gadolinium chloride