Comparative Analysis of the Transcriptome, Proteome, and miRNA Profile of Kupffer Cells and Monocytes.

Andrey Elchaninov,Evgenia Kananykhina,Anastasiya Poltavets,Anastasia Lokhonina,Irina Arutyunyan,Polina Vishnyakova,Maria Nikitina,Timur Fatkhudinov,Andrey Makarov,Galina Bolshakova,Evgeny Karpulevich,Gennady Sukhikh,Sergey Kovalchuk

doi:10.3390/biomedicines8120627

Abstract

Macrophage populations in most mammalian organs consist of cells of different origin. Resident macrophages originate from erythromyeloid precursors of the yolk sac wall; maintenance of the numbers of such macrophages in postnatal ontogenesis is practically independent of bone marrow haematopoiesis. The largest populations of the resident macrophages of embryonic origin are found in the central nervous system (microglia) and liver (Kupffer cells). In contrast, skin dermis and mucous membranes become predominantly colonized by bone marrow-derived monocytes that show pronounced functional and phenotypic plasticity. In the present study, we compared Kupffer cells and monocytes using the immunophenotype, gene expression profile, proteome, and pool of microRNA. The observed differences did not consider the resident liver macrophages as purely M2 macrophages or state that monocytes have purely M1 features. Monocytes show signs of high plasticity and sensitivity to pathogen-associated molecular patterns (e.g., high levels of transcription for Tlr 2, 4, 7, and 8). In contrast, the resident liver macrophages were clearly involved in the regulation of specific organ functions (nitrogen metabolism, complement system protein synthesis).

Highlights

The role of macrophages in the maintenance of tissue and cellular homeostasis is difficult to overestimate
The results indicated that Kupffer cells differ from monocytes by the expression of several markers (Figure 1A–E, Table 1)
The resulting cell pellets were resuspended in 30 mL phosphate buffered saline (PBS) and centrifuged at 50× g for 3 min; parenchymal cells of the liver were collected in the pellet, whereas non-parenchymal cells remained in the supernatant, which was subjected to gradient centrifugation on Lympholyte-M (Cedarlane, Burlington, ON, Canada) at 1200× g for 20 min at room temperature yielding a fraction predominantly composed of Kupffer cells

Summary

Introduction

The role of macrophages in the maintenance of tissue and cellular homeostasis is difficult to overestimate. Being an important part of innate immunity, macrophages regulate their microenvironment and the life events of surrounding cells, such as proliferation, apoptosis, metabolic rate, and changes in extracellular architecture [1]. Such a variety of functions is explained by the flexibility of macrophage phenotypes and the presence of different subpopulations of macrophages within one tissue [2,3], which originate from yolk sac hemopoietic cells or from monocytes of bone marrow origin [4,5]. The highest numbers of macrophages derived from monocytes are found in mucous membranes of the digestive tract and airways [1]

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Conclusion