Transient effects of empty liposomes on hepatic macrophage populations in rats

Abstract

Liposomes have been used as a vehicle for encapsulating chemicals or toxins in toxicological studies. We investigated the transient effects of empty liposomes on hepatic macrophages by applying a single intravenous injection at a dose of 10 ml/kg body weight in 6-week-old male F344 rats. One day after injection, the numbers of hepatic macrophages reacting to CD163, CD68, Iba-1, MHC class II, Gal-3 and CD204 were significantly increased in liposome-treated rats. CD163+ Kupffer cells and CD68+ macrophages with increased phagocytic activity in hepatic lobules were most sensitive. The histological architecture of the liver was not changed following liposome injection; however, hepatocytes showed increased proliferating activity, demonstrable with proliferation marker immunostaining and by an increase in gene profiles related to the cell cycle. In the liposome-treated rats, interestingly, AST and ALT values were significantly decreased, and MCP-1, IL-1β and TGF-β1 mRNAs were significantly increased. Collectively, the present study found that hepatic macrophages activated by liposomes can influence liver homeostasis. This information would be useful for background studies on liposomes.

Islet Macrophages Shift to a Reparative State following Pancreatic Beta-Cell Death and Are a Major Source of Islet Insulin-like Growth Factor-1

“…No differences in TUNEL + islet cells or pHH3 + islet cells were observed between groups ( Figures S4C and S4D). Effects of PBS-liposomes were consistent with a previously described effect of liposomes themselves on macrophage function (Ma et al, 2011;Pervin et al, 2016), or might have been due to macrophage depletion with PBS-liposomes (Weisser et al, 2011). These data show that islet macrophages help maintain beta-cell insulin secretion.…”

Histopathological Analysis of Rat Hepatotoxicity Based on Macrophage Functions: in Particular, an Analysis for Thioacetamide-induced Hepatic Lesions

“…It is interesting to note that clodoranete treatment induces hepatic macrophage depletion without histopathological lesions, resulting in increased values of AST and ALT 43) . As mentioned above, AST and ALT values are decreased under hepatic macrophage activation 24,40) . In liver homeostasis, the conditions of hepatic macrophages influence AST and ALT values, suggesting that hepatic macrophages participate in clearance of these hepatic deviation enzymes 17,46) .…”

“…There would be chemicals capable of activating or inhibiting hepatic macrophage functions as an initial toxicity. Novel pathogenesis may be brought out in relation to hepatic macrophage functions 40,43) . The analysis of macrophage conditions in rat toxicity studies would lead to refinement of hazard characterization.…”

“…On the other hand, regardless the presence of hepatic macrophages (approximately 20% occupation) in the liver, there is little information on hepatic macrophage-related hepatocyte damage in hepatotoxicity. As aforementioned, macrophages play important roles in liver homeostasis and have heterogeneous functions depending on microenvironments 40,43) . Importantly, infiltrating macrophages can induce tissue injury by producing cytotoxic factors, indicating the presence of pathogenesis of hepatic macrophage-mediated hepatocyte injury, or the enhancement of chemical-induced hepatocyte injury by macrophages 53) .…”

Effects of dexamethasone on hepatic macrophages in normal livers and thioacetamide-induced acute liver lesions in rats

“…Generally, macrophages including blood monocyte-derived macrophages, tissue resident macrophages (histiocytes/Kupffer cells) and antigen-presenting macrophages (dendritic cells) play important roles in tissue homeostasis and pathological lesion development. We previously showed that administration with empty liposome, which can be ingested by macrophages, activates Kupffer cells in rats; interestingly, the treated rats showed decreased values of serum hepatic deviation enzymes, although there were no observable changes in histological structures 1 . Kupffer cells may be responsible for liver homeostasis.…”