Neutrophil extracellular traps (NETs) trap and kill pathogens very efficiently but also activate dendritic cells and prime T cells. Previously, we demonstrated that neutrophils are primed and circulating NETs are elevated in relapsing remitting multiple sclerosis (RRMS), a T cell-mediated autoimmune disease. Here, we demonstrate gender specific differences in circulating NETs but not in neutrophil priming in RRMS patients. Although the results from our systematic and in depth characterization of these patients argue against a major role of circulating NETs in this disease, they suggest that NETs may underlie gender-specific differences in MS pathogenesis.
Abstract (100 words)Neutrophil extracellular traps (NETs) trap and kill pathogens very efficiently but also activate dendritic cells and prime T cells. Previously, we demonstrated that neutrophils are primed and circulating NETs are elevated in relapsing remitting multiple sclerosis (RRMS), a T cell-mediated autoimmune disease. Here, we demonstrate gender specific differences in circulating NETs but not in neutrophil priming in RRMS patients. Although the results from our systematic and in depth characterization of these patients argue against a major role of circulating NETs in this disease, they suggest that NETs may underlie gender-specific differences in MS pathogenesis.Key words: Neutrophil, neutrophil extracellular traps (NETs), multiple sclerosis, genderCirculating NETs in MS patients 3
1-IntroductionThe main function of the innate immune system during infection is to eliminate the pathogen, and neutrophils are key players in innate immune responses.Women of reproductive age are more resistant to sepsis and subsequent morbidity and mortality than men (Schroder et al., 1998), and the incidence of sepsis in postmenopausal women increases to levels almost equal to those seen in age-matched men (Martin et al., 2003). Women also have a higher systemic neutrophil count compared with men (Bain and England, 1975a), and neutrophil counts correlate with estradiol levels during menstruation (Bain and England, 1975b) and pregnancy (Efrati et al., 1964) suggesting that sex hormones influence neutrophilia and overall resistance to sepsis most likely by delaying apoptosis in neutrophils (Molloy et al., 2003). In order to eliminate pathogens during infections, neutrophils are armed with a variety of weapons including engulfment and intracellular degradation of microbes (Hampton et al., 1998;Segal, 2005), release of oxygen species and granule proteins (Lehrer and Ganz, 1999) and release of extracellular chromatin fibers bound to granular, nuclear and cytoplasmic proteins called neutrophil extracellular traps (NETs) (Brinkmann et al., 2004). NETs not only trap and kill pathogens very efficiently but also minimize collateral tissue damage by containing proteases to the DNA fibers and act as physical barriers preventing microbial spread. Despite the well documented importance of NETs as an effective antimicrobial first line defense mechanism, there is increasing ...
