Piroptoza

Piroptoza je visokoupalni oblik lizne programirane ćelijske smrti koji se najčešće javlja nakon infekcije unutarćelijskim patogenima i vjerovatno je dio antimikrobnog odgovora . Ovaj proces podstiče brzo uklanjanje različitih bakterijskih, virusnih, gljivičnih i protozojskih infekcija, uklanjanjem unutarćelijskih replikacijskih niša i jačanjem odbrambenih odgovora domaćina. Piroptoza se može desiti u imunskim ćelijama, a takođe se navodi da se javlja u keratinocitima i nekim epitelnim ćelijama.^[1] Proces se pokreće formiranjem velikog supramolekulskog kompleksa zvanog inflamasom (također poznatog kao piroptozom) nakon signala unutarćelijske opasnosti.^[2] Inflamasom aktivira drugačiji skup kaspaza u poređenju sa apoptozom, naprimjer, kaspaza-1/4/5 kod ljudi i kaspaza-11 kod miševa.^[3] Ove kaspaze doprinose sazrevanju i aktivaciji nekoliko proupalnih citokina i proteina koji formiraju pore gasdermina. Formiranje pora uzrokuje rupturu ćelijske membrane i oslobađanje citokina, kao i različitih molekulskih uzoraka povezanih s oštećenjem (DAMP), molekula kao što su HMGB-1, ATP i DNK, van ćelije. Ove molekule regrutuju više imunskih ćelija i dalje održavaju upalnu kaskadu u tkivu.^[4]^[5]

Međutim, kod patogenih hroničnih bolesti, upalni odgovor ne eliminira primarni stimulus. Pojavljuje se hronični oblik upale koja u konačnici doprinosi oštećenju tkiva. Piroptoza je povezana sa bolestima, uključujući rak, neurodegeneraciju i bolesti kardiovaskularnog sistema. Neki primjeri piroptoze uključuju makrofage inficirane salmonelama i abortivno HIV-inficirane T-pomoćne ćelije.^[6]^[7]^[8]

^ Jorgensen I, Miao EA (maj 2015). "Pyroptotic cell death defends against intracellular pathogens". Immunological Reviews. 265 (1): 130–42. doi:10.1111/imr.12287. PMC 4400865. PMID 25879289.
^ Nirmala JG, Lopus M (april 2020). "Cell death mechanisms in eukaryotes". Cell Biology and Toxicology. 36 (2): 145–164. doi:10.1007/s10565-019-09496-2. PMID 31820165. S2CID 208869679.
^ Gong W, Shi Y, Ren J (mart 2020). "Research progresses of molecular mechanism of pyroptosis and its related diseases". Immunobiology. 225 (2): 151884. doi:10.1016/j.imbio.2019.11.019. PMID 31822435. S2CID 209314359.
^ Baroja-Mazo A, Martín-Sánchez F, Gomez AI, Martínez CM, Amores-Iniesta J, Compan V, et al. (august 2014). "The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response". Nature Immunology. 15 (8): 738–48. doi:10.1038/ni.2919. PMID 24952504. S2CID 6928042.
^ Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G, et al. (august 2014). "The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation". Nature Immunology. 15 (8): 727–37. doi:10.1038/ni.2913. PMC 4116676. PMID 24952505.
^ Fink SL, Cookson BT (novembar 2006). "Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages". Cellular Microbiology. 8 (11): 1812–25. doi:10.1111/j.1462-5822.2006.00751.x. PMID 16824040.
^ Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, et al. (januar 2014). "Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection". Nature. 505 (7484): 509–14. Bibcode:2014Natur.505..509D. doi:10.1038/nature12940. PMC 4047036. PMID 24356306.
^ Doitsh G, Greene WC (mart 2016). "Dissecting How CD4 T Cells Are Lost During HIV Infection". Cell Host & Microbe. 19 (3): 280–91. doi:10.1016/j.chom.2016.02.012. PMC 4835240. PMID 26962940.

[pyro1-1] Jorgensen I, Miao EA (maj 2015). "Pyroptotic cell death defends against intracellular pathogens". Immunological Reviews. 265 (1): 130–42. doi:10.1111/imr.12287. PMC 4400865. PMID 25879289.

[pmid31820165-2] Nirmala JG, Lopus M (april 2020). "Cell death mechanisms in eukaryotes". Cell Biology and Toxicology. 36 (2): 145–164. doi:10.1007/s10565-019-09496-2. PMID 31820165. S2CID 208869679.

[Gong-3] Gong W, Shi Y, Ren J (mart 2020). "Research progresses of molecular mechanism of pyroptosis and its related diseases". Immunobiology. 225 (2): 151884. doi:10.1016/j.imbio.2019.11.019. PMID 31822435. S2CID 209314359.

[4] Baroja-Mazo A, Martín-Sánchez F, Gomez AI, Martínez CM, Amores-Iniesta J, Compan V, et al. (august 2014). "The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response". Nature Immunology. 15 (8): 738–48. doi:10.1038/ni.2919. PMID 24952504. S2CID 6928042.

[5] Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G, et al. (august 2014). "The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation". Nature Immunology. 15 (8): 727–37. doi:10.1038/ni.2913. PMC 4116676. PMID 24952505.

[Fink_2006-6] Fink SL, Cookson BT (novembar 2006). "Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages". Cellular Microbiology. 8 (11): 1812–25. doi:10.1111/j.1462-5822.2006.00751.x. PMID 16824040.

[Doitsh_2014-7] Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, et al. (januar 2014). "Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection". Nature. 505 (7484): 509–14. Bibcode:2014Natur.505..509D. doi:10.1038/nature12940. PMC 4047036. PMID 24356306.

[8] Doitsh G, Greene WC (mart 2016). "Dissecting How CD4 T Cells Are Lost During HIV Infection". Cell Host & Microbe. 19 (3): 280–91. doi:10.1016/j.chom.2016.02.012. PMC 4835240. PMID 26962940.

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