title: Neutrophils from chronic lymphocytic leukemia patients exhibit an increased capacity to release extracellular traps (NETs).
abstract: 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.
authors: Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
authors: Enrique
authors: E
authors: Podaza
authors: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina.
authors: Florencia
authors: F
authors: Sabbione
authors: Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
authors: Denise
authors: D
authors: Risnik
authors: Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
authors: Mercedes
authors: M
authors: Borge
authors: Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
authors: María B
authors: MB
authors: Almejún
authors: Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
authors: Ana
authors: A
authors: Colado
authors: Servicio de Hematología, Sanatorio Municipal Dr. Julio Méndez, Buenos Aires, Argentina.
authors: Horacio
authors: H
authors: Fernández-Grecco
authors: Servicio de Hematología, Sanatorio Municipal Dr. Julio Méndez, Buenos Aires, Argentina.
authors: María
authors: M
authors: Cabrejo
authors: Servicio de Hematología, Hospital Municipal Dr. Teodoro Alvarez, Buenos Aires, Argentina.
authors: Raimundo F
authors: RF
authors: Bezares
authors: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina.
authors: Analía
authors: A
authors: Trevani
authors: Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
authors: Romina
authors: R
authors: Gamberale
authors: Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina. giordanomirta@gmail.com.
authors: Mirta
authors: M
authors: Giordano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D065206:Extracellular Traps / Q000276:immunology*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000276:immunology*; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*
chemical_list: D016209:Interleukin-8
keywords: Chronic lymphocytic leukemia; Infections; Interleukin 8 (IL-8); Neutrophil; Neutrophil extracellular traps