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000095411 005__ 20210902121751.0
000095411 0247_ $$2doi$$a10.3389/fimmu.2020.01054
000095411 0248_ $$2sideral$$a118936
000095411 037__ $$aART-2020-118936
000095411 041__ $$aeng
000095411 100__ $$aGarzon-Tituana, M
000095411 245__ $$aThe Multifaceted Function of Granzymes in Sepsis: Some Facts and a Lot to Discover
000095411 260__ $$c2020
000095411 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095411 5203_ $$aSepsis is a serious global health problem. In addition to a high incidence, this syndrome has a high mortality and is responsible for huge health expenditure. The pathophysiology of sepsis is very complex and it is not well-understood yet. However, it is widely accepted that the initial phase of sepsis is characterized by a hyperinflammatory response while the late phase is characterized by immunosuppression and immune anergy, increasing the risk of secondary infections. Granzymes (Gzms) are a family of serine proteases classified according to their cleavage specificity. Traditionally, it was assumed that all Gzms acted as cytotoxic proteases. However, recent evidence suggests that GzmB is the one with the greatest cytotoxic capacity, while the cytotoxicity of others such as GzmA and GzmK is not clear. Recent studies have found that GzmA, GzmB, GzmK, and GzmM act as pro-inflammatory mediators. Specially, solid evidences show that GzmA and GzmK function as extracellular proteases that regulate the inflammatory response irrespectively of its ability to induce cell death. Indeed, studies in animal models indicate that GzmA is involved in the cytokine release syndrome characteristic of sepsis. Moreover, the GZM family also could regulate other biological processes involved in sepsis pathophysiology like the coagulation cascade, platelet function, endothelial barrier permeability, and, in addition, could be involved in the immunosuppressive stage of sepsis. In this review, we provide a comprehensive overview on the contribution of these novel functions of Gzms to sepsis and the new therapeutic opportunities emerging from targeting these proteases for the treatment of this serious health problem.
000095411 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B29$$9info:eu-repo/grantAgreement/ES/ISCIII/PI16-00526$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1-R
000095411 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000095411 590__ $$a7.561$$b2020
000095411 591__ $$aIMMUNOLOGY$$b24 / 162 = 0.148$$c2020$$dQ1$$eT1
000095411 592__ $$a2.645$$b2020
000095411 593__ $$aImmunology and Allergy$$c2020$$dQ1
000095411 593__ $$aImmunology$$c2020$$dQ1
000095411 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095411 700__ $$aArias, MA
000095411 700__ $$0(orcid)0000-0002-8796-2717$$aSierra-Monzon, JL$$uUniversidad de Zaragoza
000095411 700__ $$aMorte-Romea, E
000095411 700__ $$0(orcid)0000-0002-1861-5981$$aSantiago, L$$uUniversidad de Zaragoza
000095411 700__ $$0(orcid)0000-0002-3888-7036$$aRamirez-Labrada, A
000095411 700__ $$0(orcid)0000-0003-3043-147X$$aMartinez-Lostao, L$$uUniversidad de Zaragoza
000095411 700__ $$aPano-Pardo, JR
000095411 700__ $$aGalvez, EM
000095411 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J$$uUniversidad de Zaragoza
000095411 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000095411 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000095411 773__ $$g11 (2020), 1054 [12 pp]$$pFront. immunol.$$tFRONTIERS IN IMMUNOLOGY$$x1664-3224
000095411 8564_ $$s674635$$uhttps://zaguan.unizar.es/record/95411/files/texto_completo.pdf$$yVersión publicada
000095411 8564_ $$s29687$$uhttps://zaguan.unizar.es/record/95411/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095411 909CO $$ooai:zaguan.unizar.es:95411$$particulos$$pdriver
000095411 951__ $$a2021-09-02-09:48:45
000095411 980__ $$aARTICLE