Heterogeneity of rat liver and spleen macrophages in gadolinium chloride–induced elimination and repopulation

Abstract

Blockade of phagocytosis and selective elimination of macrophages (m phi s) are generally accepted procedures for gaining knowledge about the function of m phi s in vivo. This study demonstrates that intravenous injection of gadolinium chloride (GdCl3) not only blocks phagocytosis by rat liver m phi s (Kupffer cells) but also selectively eliminates the large m phi s situated in the periportal zone of the liver acinus. Repopulation of m phi s starts at 4 days after injection. During repopulation, m phi s are less vulnerable to GdCl3. When repopulation is complete, the new m phi s show the same vulnerability as the original ones. Splenic m phi s are less vulnerable to GdCl3 because only some of the red pulp m phi s transiently disappear. The white pulp m phi s are not affected. Repopulation occurs sooner than in liver. These results indicate that administration of GdCl3 is a suitable approach to studying the in vivo function of large Kupffer cells.

The role of tissue macrophages in the induction of proinflammatory cytokine production following intravenous injection of lipoplexes

“…Several studies have reported that intravenous injection of GdCl 3 , a rare earth metal salt, is able to not only block the phagocytosis of macrophages in liver and spleen, but also eliminate them and that a single injection of GdCl 3 blocks phagocytosis in more than 90% of Kupffer cells. 20,21 GdCl 3 has also been used to evaluate the function of these cells in many reports. 22,23 We report here that liver Kupffer cells and spleen macrophages play an important role in the induction of proinflammatory cytokine production after intravenous administration of a lipoplex and that prevention of lipoplex uptake by these cells eliminates the refractory behavior to repeated injection.…”

“…We could not find any differences in the accumulation of lipoplex in the spleen (Figure 1c). Hardonk et al 20 reported that spleen macrophages were much less vulnerable to GdCl 3 than liver Kupffer cells. Only some of the red pulp macrophages of the spleen transiently disappeared and the macrophages in the white pulp were not affected.…”

Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia

“…GdCl 3 (Sigma-Aldrich) has previously been shown to block phagocytosis by liver Kupfer cells within 24 to 48 hours after intravenous infusion and to selectively eliminate large macrophages situated in the periportal zone of the liver acinus. 35,36 Isofluorane anesthetized mice were injected intra-orbitally with GdCl 3 (50 mg/kg) or an equal volume of 0.15 M NaCl, and platelets and monocytes were enumerated as above. …”

Kupffer cells and macrophages are not required for hepatic hepcidin activation during iron overload†

“…This agent inhibits phagocytosis and selectively eliminates liver macrophages while reducing cytokine and free radical production by Kupffer cells in response to injury. [17][18][19] The results indicate that Kupffer cells in vivo and macrophages ex vivo are essential for hepcidin expression in hepatocytes in response to inflammatory stimuli but are not required for iron activation. This finding has important implications for understanding the role of hepcidin in physiology but also in pathophysiological states such as hereditary hemochromatosis (HH).…”