MARCO+ Macrophage Dynamics in Regenerating Liver after 70% Liver Resection in Mice

Abstract

Background: Macrophages play a key role in liver regeneration. The fates of resident macrophages after 70% resection are poorly investigated. In this work, using the MARCO macrophage marker (abbreviated from macrophage receptor with collagenous structure), we studied the dynamics of mouse liver resident macrophages after 70% resection. Methods: In BALB/c male mice, a model of liver regeneration after 70% resection was reproduced. The dynamics of markers CD68, TIM4, and MARCO were studied immunohistochemically and by using a Western blot. Results: The number of MARCO- and CD68-positive macrophages in the regenerating liver increased 1 day and 3 days after resection, respectively. At the same time, the content of the MARCO protein increased in the sorted macrophages of the regenerating liver on the third day. Conclusions: The data indicate that the number of MARCO-positive macrophages in the regenerating liver increases due to the activation of MARCO synthesis in the liver macrophages. The increased expression of MARCO by macrophages can be regarded as a sign of their activation. In the present study, stimulation with LPS led to an increase in the expression of the Marco gene in both Kupffer cells and macrophages of bone marrow origin.

An Eye on Kupffer Cells: Development, Phenotype and the Macrophage Niche

“…Our own data obtained in a model of 70% liver resection in mice indicate that Tim4 expression in hepatic tissues can rapidly increase in the remnant liver tissue. This increase can be attributed to the influence of boosted endotoxin/LPS blood levels, and this suggestion has been supported by in vitro experiments [ 113 ]. Notably, KCs isolated from the intact liver by magnetic sorting for F4/80 had Tim4 expression levels similar to macrophages differentiated from peripheral blood monocytes isolated by magnetic sorting for CD115 and cultured with M-CSF.…”

“…Considering the reduced Tim4 expression in the ‘newcomers’ [ 61 ], it would be reasonable to expect decreased expression of TIM4 marker in total liver macrophages after resection. However, this proved not to be the case, apparently due to the stimulating effect of LPS on the new, differentiating monocytic macrophages [ 113 ]. It can be concluded that, in this setting, Tim4 expression levels depend more on LPS exposure than on the length of residence in the macrophage niche of KCs [ 113 ].…”

“…However, this proved not to be the case, apparently due to the stimulating effect of LPS on the new, differentiating monocytic macrophages [ 113 ]. It can be concluded that, in this setting, Tim4 expression levels depend more on LPS exposure than on the length of residence in the macrophage niche of KCs [ 113 ].…”

“…However, the latter point is questionable, considering the long-known role of this receptor in antimicrobial immunity [ 114 , 115 ]. True enough, KCs and bone marrow-derived macrophages express Marco at different levels; however, a sharp increase in Marco expression at both mRNA and protein levels in the liver remnant was observed after 70% hepatectomy, and this effect was reproduced by in vitro exposure of liver macrophage cultures to LPS [ 113 ]. Such dynamics of MARCO expression are consistent with its being a marker of pro-inflammatory state in murine macrophages [ 103 ].…”

Macrophages in Health and Non-Infectious Disease 2.0

“…The expression of the MARCO gene (as well as some other markers) in macrophages originating from liver after a resection procedure was investigated, with a conclusion regarding the increase in MARCO in these cells upon regeneration of liver in a mouse model [ 12 ].…”