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Open Access 01-10-2011 | Research

Critical illness induces alternative activation of M2 macrophages in adipose tissue

Authors: Lies Langouche, Mirna B Marques, Catherine Ingels, Jan Gunst, Sarah Derde, Sarah Vander Perre, André D'Hoore, Greet Van den Berghe

Published in: Critical Care | Issue 5/2011

Abstract

Introduction

We recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown.

Methods

We studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n = 20) and non-surviving prolonged critically ill patients (n = 61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients.

Results

Subcutaneous and visceral adipose tissue biopsies from non-surviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-α and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARγ protein levels.

Conclusions

Unlike obesity, critical illness evokes adipose tissue accumulation of alternatively activated M2 macrophages, which have local anti-inflammatory and insulin sensitizing features. This M2 macrophage accumulation may contribute to the previously observed protective metabolic activity of adipose tissue during critical illness.

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Title: Critical illness induces alternative activation of M2 macrophages in adipose tissue
Authors: Lies Langouche
Mirna B Marques
Catherine Ingels
Jan Gunst
Sarah Derde
Sarah Vander Perre
André D'Hoore
Greet Van den Berghe
Publication date: 01-10-2011
Publisher: BioMed Central
Published in: Critical Care / Issue 5/2011
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/cc10503

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Critical illness induces alternative activation of M2 macrophages in adipose tissue

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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