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

PODAZA ENRIQUE; SABBIONE FLORENCIA; RISNIK DENISE; BORGE MERCEDES; ALMEJÚN MARÍA BELÉN; COLADO ANA; FERNÁNDEZ GRECCO HORACIO; CABREJO MARÍA; BEZARES RAIMUNDO F; TREVANI ANALÍA; GAMBERALE ROMINA; GIORDANO MIRTA

CANCER IMMUNOLOGY IMMUNOTHERAPY

SPRINGER

Lugar: Berlin; Año: 2017 vol. 66 p. 77 - 89

0340-7004

Chronic lymphocytic leukemia (CLL) is characterized by immune defects that contribute to a high rate of infections and autoimmune cytopenias. Neutrophils are the first line of innate immunity and respond to pathogens through multiple mechanisms, including the release of neutrophil extracellular traps (NETs). These web-like structures composed of DNA, histones, and granular proteins are also produced under sterile conditions and play important roles in thrombosis and autoimmune disorders. Here we show that neutrophils from CLL patients are more prone to release NETs compared to those from age-matched healthy donors (HD). Increased generation of NETs was not due to higher levels of elastase, myeloperoxidase, or reactive oxygen species production. Instead, we found that plasma from CLL patients was able to prime neutrophils from HD 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 NETs release. Finally, we found that culture with NETs delayed spontaneous apoptosis and increased the expression of activation markers on leukemic B cells. Our study provides new insights into the immune dysregulation in CLL and suggests that the chronic inflammatory environment typical of CLL probably underlies this inappropriate neutrophil priming.