Dynamics of macrophage populations of the liver after subtotal hepatectomy in rats

Andrey V Elchaninov,Timur Kh Fatkhudinov,Dmitry V Goldshtein,Anastasia V Lokhonina,Galina B Bolshakova,Natalia Y Usman,Gennady T Sukhikh,Andrey V Makarov,Irina V Arutyunyan,Viktor V Surovtsev,Irina Z Eremina,Valeria V Glinkina,Evgeniya Y Kananykhina

doi:10.1186/s12865-018-0260-1

Abstract

BackgroundIn many clinical cases of extensive liver resection (e.g. due to malignancy), the residual portion is too small to maintain the body homeostasis. The resulting acute liver failure is associated with the compensatory growth inhibition, which is a typical manifestation of the ‘small for size’ liver syndrome. The study investigates possible causes of the delayed onset of hepatocyte proliferation after subtotal hepatectomy (80% liver resection) in rats.ResultsThe data indicate that the growth inhibition correlates with delayed upregulation of the Tnf gene expression and low content of the corresponding Tnfα protein within the residual hepatic tissue. Considering the involvement of Tnf/Tnfα, the observed growth inhibition may be related to particular properties of liver macrophages – the resident Kupffer cells with CD68+CX1CR3−CD11b− phenotype.ConclusionsThe delayed onset of hepatocyte proliferation correlates with low levels of Tnfα in the residual hepatic tissue. The observed growth inhibition possibly reflects specific composition of macrophage population of the liver. It is entirely composed of embryonically-derived Kupffer cells, which express the ‘proregeneratory’ M2 macrophage-specific marker CD206 in the course of regeneration.

Highlights

In many clinical cases of extensive liver resection, the residual portion is too small to maintain the body homeostasis
The first Ki67+ hepatocytes emerged at 30 h after the surgery, their numbers reached maximum at 48 h after the surgery, and decreased after that point (Fig. 1b, c, and d)
Liver macrophage population dynamics In accordance with the statement that macrophages constitute a numerous cell population in the intact liver, approx. 20% of cell nuclei observed in the sections of intact liver belonged to CD68+ cells (Fig. 2a)

Summary

Introduction

In many clinical cases of extensive liver resection (e.g. due to malignancy), the residual portion is too small to maintain the body homeostasis. Macrophages are known to participate in the coordination of tissue regeneration. They constitute a heterogeneous category of cells, which differ in their origin and functional properties [1]. Macrophages originate from three different hemopoietic cell sources: yolk sac, embryonic/fetal liver, and red bone marrow. Macrophages are a mixture of descendants from both the embryonic liver and the red bone marrow (whether hemopoietic stem cells of the yolk sac are involved remains as yet unexplored) [1]. The central nervous system and the liver comprise their own specific macrophage populations, which originate almost exclusively from the hemopoietic cells of embryonic. In addition to the multiple sources of origin, activated macrophages may differ by their functional properties. There is still no certainty about correlation of the source of origin of a macrophage with its functional type [1]

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Discussion

Conclusion