title: Decreased apopto-phagocytic gene expression in the macrophages of systemic lupus erythematosus patients.
abstract: The clearance of apoptotic cells has an important role in the maintenance of tissue homeostasis and in the protection of tissues from the inflammatory and immunogenic contents of dying cells. A defect in the recognition and phagocytosis of apoptotic cells contributes to the development of chronic inflammation and autoimmune disorders. We have observed that compared with healthy donors, differentiated macrophages from patients with untreated systemic lupus erythematosus (SLE) showed decreased phagocytosis of apoptotic neutrophils. A TaqMan Low Density Array was designed to determine the mRNA expression levels of 95 apopto-phagocytic genes in differentiated non-phagocytosing and phagocytosing macrophages. In the macrophages of clinically and immunoserologically active SLE patients, 39 genes were expressed at lower levels than in the control macrophages. When inactive patients were compared with those with minor immunoserological abnormalities or patients in an immunoserologically active state, a relationship was observed between the altered gene expression profile and the disease state. In the macrophages of patients with engulfing apoptotic cells, an upregulation of genes involved in inflammation, autophagy, and signaling was observed. These results indicate that novel immune-pathological pathways are involved in SLE and suggest targets for potential therapeutic modulation.
authors.affiliation: 1Department of Biochemistry and Molecular Biology, Apoptosis and Genomics Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Majai
authors.forename: E
authors.initials: E
authors.lastname: Kiss
authors.forename: T
authors.initials: T
authors.lastname: Tarr
authors.forename: G
authors.initials: G
authors.lastname: Zahuczky
authors.forename: Z
authors.initials: Z
authors.lastname: Hartman
authors.forename: G
authors.initials: G
authors.lastname: Szegedi
authors.forename: L
authors.initials: L
authors.lastname: Fésüs
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D002454:Cell Differentiation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008894:Milk Proteins / Q000235:genetics; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010587:Phagocytosis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D039641:Integrin beta Chains; C098942:MFGE8 protein, human; D008894:Milk Proteins; D012333:RNA, Messenger; C084344:integrin beta5
keywords: Lupus; apoptosis; autoimmunity; macrophage; phagocytosis