Transplantable subcutaneous hepatoma 22a affects functional activity of resident tissue macrophages in periphery.

Ekaterina P Kisseleva,Olga I Stepanova,Andrei V Krylov,Victoria I Lioudyno

doi:10.1155/2011/793034

Ekaterina P Kisseleva, Olga I Stepanova + Show 2 more

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https://doi.org/10.1155/2011/793034

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Abstract

Tumors spontaneously develop central necroses due to inadequate blood supply. Recent data indicate that dead cells and their products are immunogenic to the host. We hypothesized that macrophage tumor-dependent reactions can be mediated differentially by factors released from live or dead tumor cells. In this study, functional activity of resident peritoneal macrophages was investigated in parallel with tumor morphology during the growth of syngeneic nonimmunogenic hepatoma 22a. Morphometrical analysis of tumor necroses, mitoses and leukocyte infiltration was performed in histological sections. We found that inflammatory potential of peritoneal macrophages in tumor-bearing mice significantly varied depending on the stage of tumor growth and exhibited two peaks of activation as assessed by nitroxide and superoxide anion production, 5′-nucleotidase activity and pinocytosis. Increased inflammatory reactions were not followed by the enhancement of angiogenic potential as assessed by Vascular Endothelial Growth Factor mRNA expression. Phases of macrophage activity corresponded to the stages of tumor growth characterized by high proliferative potential. The appearance and further development of necrotic tissue inside the tumor did not coincide with changes in macrophage behavior and therefore indirectly indicated that activation of macrophages was a reaction mostly to the signals produced by live tumor cells.

Highlights

It is abundantly evident that innate immune response plays important role in antitumor defense [1]
After that macrophages exhibit a proinflammatory M1 phenotype which is characterized by the release of proinflammatory cytokines (IL-12, TNF-α), reactive nitrogen intermediates (NOs), and reactive oxygen intermediates (ROIs), which support their microbicidal/tumoricidal activity
We found that inflammatory potential of peritoneal macrophages in tumor-bearing mice significantly varied depending on the stage of tumor growth and exhibited two peaks of activation as assessed by abovementioned parameters

Summary

Introduction

It is abundantly evident that innate immune response plays important role in antitumor defense [1]. It was shown that macrophages play a dual role in tumor growth and can possess antitumor as well as protumor activities. They were subdivided into M1 (classically activated) or M2 (alternatively activated) phenotypes [2]. After that macrophages exhibit a proinflammatory M1 phenotype which is characterized by the release of proinflammatory cytokines (IL-12, TNF-α), reactive nitrogen intermediates (NOs), and reactive oxygen intermediates (ROIs), which support their microbicidal/tumoricidal activity. M1 macrophages promote Th1 responses and are considered to be powerful effectors against pathogens and tumor cells

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