PPARγ-dependent regulation of human macrophages in phagocytosis of apoptotic cells

Gyöngyike Majai, Z. Sarang, Krisztián Csomós, Gábor Zahuczky, L. Fésüs

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Macrophages acquire their capacity for efficient phagocytosis of apoptotic cells during their differentiation from monocytes. The peroxisome proliferator-activated receptor gamma (PPARγ) is highly up-regulated during this maturation program. We report that addition of PPARγ antagonist during differentiation of human monocytes to macrophages significantly reduced the capacity of macrophages to engulf apoptotic neutrophils, but did not influence phagocytosis of opsonized bacteria. Macrophage-specific deletion of PPARγ in mice also resulted in decreased uptake of apoptotic cells. The antagonist acted in a dose-dependent manner during the differentiation of human macrophages and could also reverse the previously observed augmentation of phagocytosis by glucocorticoids. Blocking activation of PPARγ led to down-regulation of molecular elements (CD36, AXL, TG2 and PTX3) of the engulfment process. Inhibition of PPARγ-dependent gene expression did not block the anti-inflammatory effect of apoptotic neutrophils or synthetic glucocorticoid, but significantly decreased production of IL-10 induced by LPS. Our results suggest that during differentiation of macrophages natural ligands of PPARγ are formed, regulating the expression of genes responsible for effective clearance of apoptotic cells and macrophage-mediated inflammatory responses.

Original languageEnglish
Pages (from-to)1343-1354
Number of pages12
JournalEuropean Journal of Immunology
Volume37
Issue number5
DOIs
Publication statusPublished - May 2007

Fingerprint

Cytophagocytosis
PPAR gamma
Macrophages
Phagocytosis
Glucocorticoids
Monocytes
Neutrophils
Gene Expression
Interleukin-10
Anti-Inflammatory Agents
Down-Regulation
Ligands
Bacteria

Keywords

  • Apoptosis
  • Cytokines
  • Macrophages
  • Monocytes
  • Phagocytosis

ASJC Scopus subject areas

  • Immunology

Cite this

PPARγ-dependent regulation of human macrophages in phagocytosis of apoptotic cells. / Majai, Gyöngyike; Sarang, Z.; Csomós, Krisztián; Zahuczky, Gábor; Fésüs, L.

In: European Journal of Immunology, Vol. 37, No. 5, 05.2007, p. 1343-1354.

Research output: Contribution to journalArticle

Majai, Gyöngyike ; Sarang, Z. ; Csomós, Krisztián ; Zahuczky, Gábor ; Fésüs, L. / PPARγ-dependent regulation of human macrophages in phagocytosis of apoptotic cells. In: European Journal of Immunology. 2007 ; Vol. 37, No. 5. pp. 1343-1354.
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