Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Human lupus netting neutrophils induce endothelial damage, infiltrate tissues and expose immunostimulatory molecules

ABSTRACT: Our group has proposed that low-density granulocytes (LDGs) play an important role in lupus pathogenesis, as they can damage endothelial cells and synthesize increased levels of proinflammatory cytokines and type I interferons. LDGs have a heightened capacity to synthesize neutrophil extracellular traps (NETs). NETs from LDGs display increased levels of bactericidal and immunostimulatory proteins, such as the cathelicidin LL37 and externalize double-stranded DNA (dsDNA). Lupus netting LDGs have increased capacity to kill endothelial cells and expose IL-17. Through NETosis, lupus neutrophils stimulate plasmacytoid DCs to synthesize IFN-?. Our results further expand the potential pathogenic role of aberrant lupus neutrophils through a NET-mediated effect. We used microarrays to analyze the gene expression of neutrophils in healthy and lupus patients, and of low-density granulocytes in lupus patients. Human neutrophils and LDGs were isolated from PBMCs. RNA from healthy neutrophils, lupus neutrophils and lupus LDGs was extracted and processed for hybridization on Affymetrix microarrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Celine Berthier 

PROVIDER: E-GEOD-26975 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus.

Villanueva Eneida E   Yalavarthi Srilakshmi S   Berthier Celine C CC   Hodgin Jeffrey B JB   Khandpur Ritika R   Lin Andrew M AM   Rubin Cory J CJ   Zhao Wenpu W   Olsen Stephen H SH   Klinker Matthew M   Shealy David D   Denny Michael F MF   Plumas Joel J   Chaperot Laurence L   Kretzler Matthias M   Bruce Allen T AT   Kaplan Mariana J MJ  

Journal of immunology (Baltimore, Md. : 1950) 20110525 1

An abnormal neutrophil subset has been identified in the PBMC fractions from lupus patients. We have proposed that these low-density granulocytes (LDGs) play an important role in lupus pathogenesis by damaging endothelial cells and synthesizing increased levels of proinflammatory cytokines and type I IFNs. To directly establish LDGs as a distinct neutrophil subset, their gene array profiles were compared with those of autologous normal-density neutrophils and control neutrophils. LDGs significan  ...[more]

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