Ekstacelularne mreže neutrofilnih granulocita

Abstract

Neutrophils are phagocytic cells establishing first line of defence against viruses, bacteria, fungi and protozoa. Ingestion and killing of “foreigners” or elimination of non-self molecules are complex in nature and require coordination of numerous cellular activities. As a response to injury or infection, inflammatory response is usually generated being mediated by neutrophils. These cells somehow regulate functions of other innate immune cells which is crucial for pathogen elimination. For a long time, it was beleived that neutrophils eliminates bacteria only by phagocytosis and intracellular killing including release of reactive oxigen species (ROS). Currently, a significance of their antimicrobial polypeptides is becoming more and more evident. Antimicrobial polypeptides that are released in extracellular space can participate in bacterial elimination both directly or by indirect mechanisms. As a consequnce of bacterial, fungal or protozoal infection, microbial components such as lipopolisacharides, ROS (including H2O2) and other factors, induce morphological changes in neutrophils. The main task of neutrophiles is to “catch” microorganism and prevent its spreading by circulation. Partly, this task is effected by their third role – forming of neutrophyl extracellular traps (NET). NETs consists of decondesed chromatine, carrying proteins originating from both granules and cytoplasm. In contrast to phagocytosis, that requires substantial amount of energy, NETs can trap microbes without additional energy consumption. They act longer and can also eliminate large microbs which neutrophils can not engulf. In activated neutrophils, a large amount of ROS is generated which is crucial for NETs forming. From neutrophil granules, enzymes like elastase and myeloperoxidase (MPO) are being released migrating towards cellular nucleus. In the nucleus, elastase disassembles connective histones and fragmentate nuclear envelope. In the nucleus, MPO decondensates chromatine and further degradation of histones leads to cell rupture. When, at the end, cellular membrane desintegrates, a content is released in exstracellular space forming NETs.