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GPI-defective monocytes from paroxysmal nocturnal hemoglobinuria patients show impaired in vitro dendritic cell differentiation

Authors :
Bruno Rotoli
Luigi Racioppi
Serafino Zappacosta
Giuseppe Terrazzano
Claudia Andretta
Cristina Becchimanzi
Fiorella Alfinito
Anna Maria Masci
Michela Sica
Giuseppina Ruggiero
Source :
Journal of Leukocyte Biology. 76:634-640
Publication Year :
2004
Publisher :
Oxford University Press (OUP), 2004.

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, acquired hematopoietic disorder characterized by a phosphatidylinositol (PI) glycan-A gene mutation, which impairs the synthesis of the glycosyl-PI (GPI) anchor, thus causing the absence of all GPI-linked proteins on the membrane of the clonal-defective cells. The presence of a consistent GPI-defective monocyte compartment is a common feature in PNH patients. To investigate the functional behavior of this population, we analyzed its in vitro differentiation ability toward functional dendritic cells (DCs). Our data indicate that GPI-defective monocytes from PNH patients are unable to undergo full DC differentiation in vitro after granulocyte macrophage-colony stimulating factor and recombinant interleukin (IL)-4 treatment. In this context, the GPI-defective DC population shows mannose receptor expression, high levels of the CD86 molecule, and impaired CD1a up-regulation. The analysis of lipopolysaccharide and CD40-dependent, functional pathways in these DCs revealed a strong decrease in tumor necrosis factor α and IL-12 production. Finally, GPI-defective DCs showed a severe impairment in delivering accessory signals for T cell receptor-dependent T cell proliferation.

Details

ISSN :
19383673 and 07415400
Volume :
76
Database :
OpenAIRE
Journal :
Journal of Leukocyte Biology
Accession number :
edsair.doi.dedup.....e76a61b268925e9b2c712fe106debbc9
Full Text :
https://doi.org/10.1189/jlb.1203607