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Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus.
Villanueva, Eneida; Yalavarthi, Srilakshmi; Berthier, Celine C; Hodgin, Jeffrey B; Khandpur, Ritika; Lin, Andrew M; Rubin, Cory J; Zhao, Wenpu; Olsen, Stephen H; Klinker, Matthew; Shealy, David; Denny, Michael F; Plumas, Joel; Chaperot, Laurence; Kretzler, Matthias; Bruce, Allen T; Kaplan, Mariana J.
Afiliação
  • Villanueva E; Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
J Immunol ; 187(1): 538-52, 2011 Jul 01.
Article em En | MEDLINE | ID: mdl-21613614
ABSTRACT
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 significantly overexpress mRNA of various immunostimulatory bactericidal proteins and alarmins, relative to lupus and control neutrophils. In contrast, gene profiles of lupus normal-density neutrophils do not differ from those of controls. LDGs have heightened capacity to synthesize neutrophils extracellular traps (NETs), which display increased externalization of bactericidal, immunostimulatory proteins, and autoantigens, including LL-37, IL-17, and dsDNA. Through NETosis, LDGs have increased capacity to kill endothelial cells and to stimulate IFN-α synthesis by plasmacytoid dendritic cells. Affected skin and kidneys from lupus patients are infiltrated by netting neutrophils, which expose LL-37 and dsDNA. Tissue NETosis is associated with increased anti-dsDNA in sera. These results expand the potential pathogenic roles of aberrant lupus neutrophils and suggest that dysregulation of NET formation and its subsequent responses may play a prominent deleterious role.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Endotélio Vascular / Adjuvantes Imunológicos / Infiltração de Neutrófilos / Lúpus Eritematoso Sistêmico Limite: Humans Idioma: En Revista: J Immunol Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Endotélio Vascular / Adjuvantes Imunológicos / Infiltração de Neutrófilos / Lúpus Eritematoso Sistêmico Limite: Humans Idioma: En Revista: J Immunol Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos