Neutrophils from chronic lymphocytic leukemia patients exhibit an increased capacity to release extracellular traps (NETs)

PODAZA, ENRIQUE; SABBIONE, FLORENCIA; RISNIK, DENISE; BORGE, MERCEDES; ALEMEJÚN, BELEN; COLADO, ANA; FERNÁNDEZ GRECCO, HORACIO; CABREJO, MARÍA; BEZARES, FERNANDO; TREVANI, ANALIA; GAMBERALE, ROMINA; GIORDANO, MIRTA N.

CANCER IMMUNOLOGY IMMUNOTHERAPY

SPRINGER

Lugar: Berlin; Año: 2016

0340-7004

Abstract Chronic lymphocytic leukemia (CLL) is characterizedby immune defects that contribute to a high rateof infections and autoimmune cytopenias. Neutrophils arethe first line of innate immunity and respond to pathogensthrough multiple mechanisms, including the release of neutrophilextracellular traps (NETs). These web-like structurescomposed of DNA, histones, and granular proteins arealso produced under sterile conditions and play importantroles in thrombosis and autoimmune disorders. Here weshow that neutrophils from CLL patients are more prone torelease NETs compared to those from age-matched healthydonors (HD). Increased generation of NETs was not dueto higher levels of elastase, myeloperoxidase, or reactiveoxygen species production. Instead, we found that plasmafrom CLL patients was able to prime neutrophils fromHD to generate higher amounts of NETs upon activation.Plasmatic IL-8 was involved in the priming effect since its depletion reduced plasma capacity to enhance NETsrelease. Finally, we found that culture with NETs delayedspontaneous apoptosis and increased the expression of activationmarkers on leukemic B cells. Our study providesnew insights into the immune dysregulation in CLL andsuggests that the chronic inflammatory environment typicalof CLL probably underlies this inappropriate neutrophilpriming.