Abstract
BackgroundMacrophages can differentiate into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes upon exposure to a pathogen or a cytokine microenvironment. However, M1/M2 macrophage polarization in polymicrobial sepsis has not been fully characterized.MethodsThe polarity of peritoneal exudate (PE) cells from mice that had undergone cecal ligation and puncture (CLP) and the response of those cells to lipopolysaccharide (LPS) in terms of cytokine and chemokine expression were examined.ResultsPE cells from CLP mice demonstrated a shift toward the M2 phenotype in terms of marker enzyme expression. In addition, the CLP-derived PE cells showed apparent unresponsiveness to LPS stimulation with regard to expression of pro-inflammatory cytokines such as TNF-α, while the expression of anti-inflammatory cytokines such as IL-10 was induced. Nevertheless, the CLP-PE cells failed to express M2 chemokines including chemokine (C-C motif) ligand 17 (CCL17), CCL22, and CCL24, all of which are important for T cell recruitment.ConclusionsThe results suggested that a shift of naïve monocytes/macrophages to the M2 phenotype, along with the lack of M2 chemokine expression in septic monocytes/macrophages, might be responsible for immunosuppression after sepsis.Electronic supplementary materialThe online version of this article (doi:10.1186/s40560-015-0124-1) contains supplementary material, which is available to authorized users.
Highlights
Macrophages can differentiate into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes upon exposure to a pathogen or a cytokine microenvironment
Sepsis increases the number of peritoneal exudate (PE) cells without affecting the monocyte/macrophage ratio The number of PE cells recovered from mice with cecal ligation and puncture (CLP) at 20 h after surgery was doubled compared to that from sham mice (7.4 × 106 in CLP vs. 3.7 × 106 in sham)
fluorescence-activated cell sorting (FACS) analysis revealed that the number of lymphocytes was significantly decreased in the CLP-PE cell population compared to the control, which was consistent with previously reported results [6]
Summary
Macrophages can differentiate into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes upon exposure to a pathogen or a cytokine microenvironment. Sepsis is a systemic inflammatory response to infection that can lead to organ dysfunction. It is one of the most challenging clinical problems worldwide and the leading cause of death in intensive care units [1]. After an inflammatory phase, characterized by excessive production of pro-inflammatory mediators [2], sepsis patients are thought to enter an immunosuppressive phase with impaired innate and adaptive immunity [3, 4]. Microbial products or Th1 cytokines (tumor necrosis factor [TNF] and interleukin [IL]-6) polarize monocytes/macrophages toward M1 cells, which release pro-inflammatory cytokines/chemokines that provoke inflammation and contribute to the killing of bacteria, while Th2 cell cytokines (IL-4 and IL-13) polarize monocytes/macrophages to M2 macrophages, which release anti-inflammatory cytokines/chemokines and contribute to tissue repair and remodeling [8, 9]. Suppressor of cytokine signaling (SOCS) [10] protein levels have been recently proposed as alternative markers for macrophage polarity: a high SOCS3/ SOCS1 expression ratio has been suggested as an indicator
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