Page 11 - Demo

%u010ceskoslovensk%u00e1 fyziologie 73/2025 %u010d. 2 37P%u0158EHLEDN%u00c9 %u010cL%u00c1NKYExtracelul%u00e1rne pasce neutrofilov v patogen%u00e9ze COVID-19Neutrophil extracelullar traps in the pathogenesis of COVID-19Barbora Ben%u010di%u010dov%u00e11,21%u00dastav molekul%u00e1rnej biomedic%u00edny, Lek%u00e1rska fakulta, Univerzita Komensk%u00e9ho, Bratislava, Slovensk%u00e1 republika2Katedra genetiky, Pr%u00edrodovedeck%u00e1 fakulta, Univerzita Komensk%u00e9ho, Bratislava, Slovensk%u00e1 republikaS%u00daHRNNeutrofilov%u00e9 extracelul%u00e1rne pasce (NETs) s v%u00fdzorom pavu%u010dinovej siete vznikaj%u00fa akt%u00edvnym vyl%u00fa%u010den%u00edm DNA neutrofilu spolu s hist%u00f3nmi a antimikrobi%u00e1lnymi enz%u00fdmami. Ich prim%u00e1rnou %u00falohou je zni%u010denie invaduj%u00facich patog%u00e9nov zachyten%u00edm a obklopen%u00edm cytotoxick%u00fdmi l%u00e1tkami. T%u00fato d%u00f4le%u017eit%u00fa funkciu v%u0161ak dop%u013a%u0148a za%u010darovan%u00fd cyklus z%u00e1palu, ak sa NETs r%u00fdchlo neodstr%u00e1nia, %u010di u%u017e pri infek%u010dn%u00fdch alebo in%u00fdch z%u00e1palov%u00fdch chorob%u00e1ch. Nedostato%u010dn%u00e1 degrad%u00e1cia vytvoren%u00fdch NETs toti%u017e indukuje ich %u010fal%u0161iu tvorbu. Pand%u00e9mia COVID-19 sp%u00f4soben%u00e1 v%u00edrusom SARS-CoV-2 uk%u00e1zala, ako variabiln%u00e1 m%u00f4%u017ee by%u0165 imunitn%u00e1 odpove%u010f na infekciu %u2013 od mierneho, %u010di dokonca asymptomatick%u00e9ho priebehu a%u017e po %u0165a%u017ek%u00fd priebeh s vysokou mortalitou sp%u00f4sobenou neadekv%u00e1tnou z%u00e1palovou odpove%u010fou s cytok%u00ednovou b%u00farkou. Viacer%u00e9 %u0161t%u00fadie pritom nazna%u010dili a nesk%u00f4r aj potvrdili, %u017ee %u0165a%u017ek%u00fd priebeh COVID-19 s%u00favis%u00ed s vy%u0161%u0161ou produkciou NETs. Ich %u00faloha v patogen%u00e9ze COVID-19 v%u0161ak nes%u00favis%u00ed len s ich proz%u00e1palov%u00fdmi vlastnos%u0165ami, ale aj s indukciou imunotromb%u00f3zy. Tvorba zrazen%u00edn vysvet%u013euje nielen vysok%u00fa celkov%u00fa mortalitu, ale aj n%u00edzku efektivitu umelej p%u013e%u00facnej ventil%u00e1cie pri okl%u00fazii p%u013e%u00facnych kapil%u00e1r. Cie%u013eom tejto pr%u00e1ce je sumarizova%u0165 poznatky o zapojen%u00ed extracelul%u00e1rnej DNA a NETs v patogen%u00e9ze COVID-19. K%u013e%u00fa%u010dov%u00e9 slov%u00e1: extracelul%u00e1rne pasce neutrofilov, SARS-CoV-2, steriln%u00fd z%u00e1pal, imunotromb%u00f3zaSUMMARYNeutrophil extracellular traps (NETs) with the appearance of spider web are formed by the active expulsion of neutrophil DNA along with histones and antimicrobial enzymes. Their primary role is to destroy invading pathogens by trapping and surrounding them with cytotoxic agents. This important function is enriched by a vicious cycle of inflammation, if NETs are not rapidly cleared whether in infectious or other inflammatory diseases. Insufficient degradation of NETs induces their further formation. COVID-19 pandemics caused by the SARS-CoV-2 virus showed how variable immune response can be- from mild or even asymptomatic to severe with high mortality caused by inappropriate inflammatory response with so-called cytokine storm. Several studies have suggested and later confirmed that severe illness is associated with higher production of NETs. Their role in the pathogenesis of COVID-19 is not associated only with their proinflammatory properties but also with the induction of so-called immunothrombosis. Clot formation explains not only the high mortality but also the low efficiency of artificial lung ventilation in pulmonary capillary occlusion. The aim of this work is to summarize knowledge about the involvement of extracellular DNA and NETs in the pathogenesis of COVID-19. Keywords: neutrophil extracellular traps, SARS-CoV-2, sterile inflammation, immunothrombosis1. EXTRACELUL%u00c1RNE PASCE NEUTROFILOV (NETS)Extracelul%u00e1rne pasce neutrofilov (NETs) s%u00fa %u0161trukt%u00fary vytv%u00e1ran%u00e9 neutrofiln%u00fdmi granulocytmi patriacimi do rodiny polymorfonukle%u00e1rnych leukocytov. %u00dalohou neutrofilov v krvnom rie%u010disku je neust%u00e1la kontrola stavu organizmu, pr%u00edtomnosti z%u00e1palu alebo vniknut%u00fdch patog%u00e9nov sp%u00f4sobuj%u00facich infekcie. Produkcia NETs je odpove%u010fou neutrofilov na elimin%u00e1ciu mikrobi%u00e1lnej inv%u00e1zie popri vyu%u017e%u00edvan%u00ed fagocyt%u00f3zy a priamej degranul%u00e1cie (Vorobjeva a Chernyak, 2020). Extracelul%u00e1rne pasce neutrofilov (NETs) sa vo svojej %u0161trukt%u00fare vyzna%u010duj%u00fa obsahom DNA, ktor%u00e1 je na podnet akt%u00edvne vyp%u00fa%u0161%u0165an%u00e1 z bunky vo forme oddelen%u00fdch chromat%u00ednov%u00fdch vl%u00e1kien pripom%u00ednaj%u00facich pavu%u010dinov%u00fa sie%u0165 (obr. 1). Tieto extracelul%u00e1rne siete s%u00fa doplnen%u00e9 pr%u00edtomnos%u0165ou hist%u00f3nov a antimikrobi%u00e1lnych prote%u00ednov derivovan%u00fdch z azurofiln%u00fdch gran%u00fal, ako s%u00fa neutrofilov%u00e1 elast%u00e1za (NE), myeloperoxid%u00e1za (MPO), kateps%u00edn G, laktofer%u00edn, kalprotekt%u00edn, katelicid%u00edn a in%u00e9 (Brinkmann et al., 2004; Urban et al., 2009). Brinkmann et al. (2004) priniesli d%u00f4kaz o existencii NETs vytvoren%u00fdch aktivovan%u00fdmi neutrofilmi, ktor%u00e9 boli schopn%u00e9 do svojich vl%u00e1kien zachyti%u0165 r%u00f4zne druhy bakt%u00e9ri%u00ed, zabr%u00e1ni%u0165 ich %u010fal%u0161ej propag%u00e1cii a z%u00e1rove%u0148 ich vysokou koncentr%u00e1ciou l%u00e1tok uvo%u013enen%u00fdch z gran%u00fal usmrti%u0165. Okrem usmrcovania bakt%u00e9ri%u00ed dok%u00e1%u017eu NETs tie%u017e eliminova%u0165 kvasinky, ktor%u00e9 s%u00fa vzh%u013eadom na svoju ve%u013ekos%u0165 odstr%u00e1nen%u00e9 efekt%u00edvnej%u0161ie ako fagocyt%u00f3zou (Urban et al., 2006).1.1 Proces NET%u00f3zyNETs s%u00fa neutrofilmi akt%u00edvne vytv%u00e1ran%u00e9 v procese zvanom NET%u00f3za, %u010do je ozna%u010denie pre typ bunkovej smrti, pri ktorej doch%u00e1dza k uvo%u013eneniu NETs z bunky. Fuchs et al. (2007) pop%u00edsal priebeh NET%u00f3zy ako proces zah%u0155%u0148aj%u00faci stratu organel a postupn%u00fa dekondenz%u00e1ciu chromat%u00ednovej %u0161trukt%u00fary jadra. Uvo%u013enen%u00e9 granul%u00e1rne a cytoplazmatick%u00e9 zlo%u017eky sa v%u010faka naru%u0161eniu jadrov%u00fdch a granul%u00e1rnych membr%u00e1n dost%u00e1vaj%u00fa do bl%u00edzkeho kontaktu s chromat%u00ednom. Zmeny t%u00fdkaj%u00face sa morfologickej %u0161trukt%u00fary neutrofilov po aktiv%u00e1cii forbol 12-myrist%u00e1t 13-acet%u00e1tom (PMA), odli%u0161n%u00e9 ako pozorovan%u00e9