GADOLINIUM CHLORIDE ALTERS THE ACINAR DISTRIBUTION OF PHAGOCYTOSIS AND BALANCE BETWEEN PROINFLAMMATORY AND ANTIINFLAMMATORY CYTOKINES

Gadolinium chloride (GdCl3) is commonly used to deplete the liver of K upffer cells (KC) and has been shown to decrease hepatic phagocytic ac tivity and to abolish hepatic expression of certain KC-specific antige ns, However, the exact fate of the KCs after GdCl3 treatment remains u nclear. To determine if GdCl3 actually decreases the total number of K Cs in the liver, we labeled phagocytically-active KC by administering fluorescent-labeled latex beads to rats treated with either normal sal ine or GdCl3. Total hepatic fluorescence and the distribution of fluor escence within liver acini were evaluated by intravital microscopy. He patic mRNA levels of KCR, a KC-specific gene product, and Pu-1, a ubiq uitous 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) cytok ines were assessed by reverse-transcriptase polymerase chain reaction (RT-PCR), Our results indicate that GdCl3 does not significantly reduc e the number of phagocytically active cells in the liver, but alters t he 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. GdC l3 pretreatment inhibited stress-related induction of IL-10, but faile d to down-regulate expression of TNF-alpha. This phenotypic change is likely to have important consequences because it permits relative over expression of TNF-alpha.