Palabras clave
Isoformas
Inflamación
Citocinas
Cómo citar
Resumen
La proteína C reactiva (CRP) es una proteína inflamatoria de fase aguda principalmente sintetizada por los hepatocitos. Se caracteriza por ser pentamérica (pCRP) que consiste en la estructura cíclica que puede disociarse en cinco monómeros separados, denominada monómerica (mCRP), ambas isoformas tienen propiedades biológicas distintas, la pCRP desarrolla actividades antiinflamantorias en comparación con mCRP. Por otro lado, un cambio estructural mediado por la interacción de pCRP con microvesículas o debido al pH ácido se produce pCRP* que es la isoforma más abundante en tejido inflamado. El presente trabajo es una revisión de la literatura con el objetivo de conocer el papel de las isoformas de la CRP y sus implicaciones en el proceso inflamatorio. En el cuál, pudimos conocer que el depósito de estas isoformas proinflamatorias agrava la respuesta inflamatoria preexistente al inducir la interacción patológica leucocito-endotelio y la generación de especies reactivas de oxígeno (EROS). La CRP actúa como marcador y participa en el proceso inflamatorio tras la activación de la vía clásica del complemento, apoptosis, liberación de óxido nítrico (NO) y su producción de citocinas proinflamatorias, como IL-6 y TNF-α.
Citas
Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Frontiers In Immunology [Internet]. 2018 abr 13;9. Disponible en: https://doi.org/10.3389/fimmu.2018.00754
Pathak A, Agrawal A. Evolution of C-Reactive Protein. Frontiers In Immunology [Internet]. 2019 abr 30;10. Disponible en: https://doi.org/10.3389/fimmu.2019.00943
Macintyre S, Samols D, Dailey P. Two carboxylesterases bind C-reactive protein within the endoplasmic reticulum and regulate its secretion during the acute phase response. Journal Of Biological Chemistry [Internet]. 1994 sep 1;269(39):24496-24503. Disponible en: https://doi.org/10.1016/s0021-9258(19)51111-5
Gaboriaud C, Juanhuix J, Gruez A, Lacroix M, Darnault C, Pignol D, Verger D, Fontecilla-Camps JC, Arlaud GJ. The Crystal Structure of the Globular Head of Complement Protein C1q Provides a Basis for Its Versatile Recognition Properties. Journal Of Biological Chemistry [Internet]. 2003 nov 1;278(47):46974-46982. Disponible en: https://doi.org/10.1074/jbc.m307764200
Hage FG, Szalai AJ. C-Reactive Protein Gene Polymorphisms, C-Reactive Protein Blood Levels, and Cardiovascular Disease Risk. Journal Of The American College Of Cardiology [Internet]. 2007 sep 1;50(12):1115-1122. Disponible en: https://doi.org/10.1016/j.jacc.2007.06.012
Potempa LA, Maldonado BA, Laurent P, Zemel ES, Gewurz H. Antigenic, electrophoretic and binding alterations of human C-reactive protein modified selectively in the absence of calcium. Molecular Immunology [Internet]. 1983 nov 1;20(11):1165-1175. Disponible en: https://doi.org/10.1016/0161-5890(83)90140-2
Khreiss T, JóZsef L, Potempa LA, Filep JG. Opposing Effects of C-Reactive Protein Isoforms on Shear-Induced Neutrophil-Platelet Adhesion and Neutrophil Aggregation in Whole Blood. Circulation [Internet]. 2004 oct 26;110(17):2713-2720. Disponible en: https://doi.org/10.1161/01.cir.0000146846.00816.dd
Braig D, Nero TL, Koch HG, Kaiser B, Wang X, Thiele JR, Morton CJ, Zeller J, Kiefer J, Potempa LA, Mellett NA, Miles LA, Du XJ, Meikle PJ, Huber-Lang M, Stark GB, Parker MW, Peter K, Eisenhardt SU. Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites. Nature Communications [Internet]. 2017 ene 23;8(1). Disponible en: https://doi.org/10.1038/ncomms14188
Hammond DJ, Singh SK, Thompson JA, Beeler BW, Rusiñol AE, Pangburn MK, Potempa LA, Agrawal A. Identification of Acidic pH-dependent Ligands of Pentameric C-reactive Protein. Journal Of Biological Chemistry [Internet]. 2010 nov 1;285(46):36235-36244. Disponible en: https://doi.org/10.1074/jbc.m110.142026
Thiele JR, Habersberger J, Braig D, Schmidt Y, Goerendt K, Maurer V, Bannasch H, Scheichl A, Woollard KJ, Von Dobschütz E, Kolodgie F, Virmani R, Stark GB, Peter K, Eisenhardt SU. Dissociation of Pentameric to Monomeric C-Reactive Protein Localizes and Aggravates Inflammation. Circulation [Internet]. 2014 jul 1;130(1):35-50. Disponible en: https://doi.org/10.1161/circulationaha.113.007124
Li HY, Wang J, Wu YX, Zhang L, Liu ZP, Filep JG, Potempa LA, Wu Y, Ji SR. Topological Localization of Monomeric C-reactive Protein Determines Proinflammatory Endothelial Cell Responses. Journal Of Biological Chemistry/The Journal Of Biological Chemistry [Internet]. 2014 may 1;289(20):14283-14290. Disponible en: https://doi.org/10.1074/jbc.m114.555318
McFadyen JD, Kiefer J, Braig D, Loseff-Silver J, Potempa LA, Eisenhardt SU, Peter K. Dissociation of C-Reactive Protein Localizes and Amplifies Inflammation: Evidence for a Direct Biological Role of C-Reactive Protein and Its Conformational Changes. Frontiers In Immunology [Internet]. 2018 jun 12;9. Disponible en: https://doi.org/10.3389/fimmu.2018.01351
Ridker PM. Clinical Application of C-Reactive Protein for Cardiovascular Disease Detection and Prevention. Circulation [Internet]. 2003 ene 28;107(3):363-369. Disponible en: https://doi.org/10.1161/01.cir.0000053730.47739.3c
Devaraj S, Venugopal S, Jialal I. Native pentameric C-reactive protein displays more potent pro-atherogenic activities in human aortic endothelial cells than modified C-reactive protein. Atherosclerosis [Internet]. 2006 ene 1;184(1):48-52. Disponible en: https://doi.org/10.1016/j.atherosclerosis.2005.03.031
Noris M, Remuzzi G. Overview of Complement Activation and Regulation. Seminars In Nephrology [Internet]. 2013 nov 1;33(6):479-492. Disponible en: https://doi.org/10.1016/j.semnephrol.2013.08.001
Mortensen SA, Sander B, Jensen RK, Pedersen JS, Golas MM, Jensenius JC, Hansen AG, Thiel S, Andersen GR. Structure and activation of C1, the complex initiating the classical pathway of the complement cascade. Proceedings Of The National Academy Of Sciences [Internet]. 2017 ene 19;114(5):986-991. Disponible en: https://doi.org/10.1073/pnas.1616998114
Mihlan M, Stippa S, Józsi M, Zipfel PF. Monomeric CRP contributes to complement control in fluid phase and on cellular surfaces and increases phagocytosis by recruiting factor H. Cell Death And Differentiation [Internet]. 2009 ago 14;16(12):1630-1640. Disponible en: https://doi.org/10.1038/cdd.2009.103
Ji SR, Ma L, Bai CJ, Shi JM, Li HY, Potempa LA, Filep JG, Zhao J, Wu Y. Monomeric C‐reactive protein activates endothelial cellsviainteraction with lipid raft microdomains. The FASEB Journal [Internet]. 2009 ene 9;23(6):1806-1816. Disponible en: https://doi.org/10.1096/fj.08-116962
Li HY, Wang J, Wu YX, Zhang L, Liu ZP, Filep JG, Potempa LA, Wu Y, Ji SR. Topological Localization of Monomeric C-reactive Protein Determines Proinflammatory Endothelial Cell Responses. Journal Of Biological Chemistry/The Journal Of Biological Chemistry [Internet]. 2014 may 1;289(20):14283-14290. Disponible en: https://doi.org/10.1074/jbc.m114.555318
Wu Y, Pan W, Hu X, Zhang A, Wei W. The prospects for targeting FcR as a novel therapeutic strategy in rheumatoid arthritis. Biochemical Pharmacology [Internet]. 2021 ene 1;183:114360.Disponible en: https://doi.org/10.1016/j.bcp.2020.114360
Devaraj S, Davis B, Simon SI, Jialal I. CRP promotes monocyte-endothelial cell adhesion via Fcγ receptors in human aortic endothelial cells under static and shear flow conditions. AJP Heart And Circulatory Physiology [Internet]. 2006 sep 1;291(3):H1170-H1176. Disponible en: https://doi.org/10.1152/ajpheart.00150.2006
Troncoso MF, Ortiz-Quintero J, Garrido-Moreno V, Sanhueza-Olivares F, Guerrero-Moncayo A, Chiong M, Castro PF, García L, Gabrielli L, Corbalán R, Garrido-Olivares L, Lavandero S. VCAM-1 as a predictor biomarker in cardiovascular disease. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease [Internet]. 2021 sep 1;1867(9):166170. Disponible en: https://doi.org/10.1016/j.bbadis.2021.166170
Regal-McDonald K, Xu B, Barnes JW, Patel RP. High-mannose intercellular adhesion molecule-1 enhances CD16+monocyte adhesion to the endothelium. AJP Heart And Circulatory Physiology [Internet]. 2019 nov 1;317(5):H1028-H1038. Disponible en: https://doi.org/10.1152/ajpheart.00306.2019
Morsing SKH, Rademakers T, Brouns SLN, Van Stalborch AMD, Donners MMPC, Van Buul JD. ADAM10-Mediated Cleavage of ICAM-1 Is Involved in Neutrophil Transendothelial Migration. Cells [Internet]. 2021 ene 25;10(2):232. Disponible en: https://doi.org/10.3390/cells10020232
Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler ME, Lobb RR. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site. Cell [Internet]. 1990 feb 1;60(4):577-584. Disponible en: https://doi.org/10.1016/0092-8674(90)90661-w
Khreiss T, JóZsef L, Potempa LA, Filep JG. Loss of Pentameric Symmetry in C-Reactive Protein Induces Interleukin-8 Secretion Through Peroxynitrite Signaling in Human Neutrophils. Circulation Research [Internet]. 2005 sep 30;97(7):690-697. Disponible en: https://doi.org/10.1161/01.res.0000183881.11739.cb
Xie L, Chang L, Guan Y, Wang X. C-Reactive Protein Augments Interleukin-8 Secretion in Human Peripheral Blood Monocytes. Journal Of Cardiovascular Pharmacology [Internet]. 2005 nov 1;46(5):690-696. Disponible en: https://doi.org/10.1097/01.fjc.0000183568.48389.a1
Saccani S, Pantano S, Natoli G. p38-dependent marking of inflammatory genes for increased NF-κB recruitment. Nature Immunology [Internet]. 2001 dic 17;3(1):69-75.Disponible en: https://doi.org/10.1038/ni748
Meniailo ME, Malashchenko VV, Shmarov VA, Gazatova ND, Melashchenko OB, Goncharov AG, Seledtsova GV, Seledtsov VI. Interleukin-8 favors pro-inflammatory activity of human monocytes/macrophages. International Immunopharmacology [Internet]. 2018 mar 1;56:217-221. Disponible en: https://doi.org/10.1016/j.intimp.2018.01.036
Zhang D, Sun M, Samols D, Kushner I. STAT3 Participates in Transcriptional Activation of the C-reactive Protein Gene by Interleukin-6. Journal Of Biological Chemistry [Internet]. 1996 abr 1;271(16):9503-9509. Disponible en: https://doi.org/10.1074/jbc.271.16.9503
Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research [Internet]. 2011 may 1;1813(5):878-888. Disponible en: https://doi.org/10.1016/j.bbamcr.2011.01.034
Weinhold B, Bader A, Poli V, Rüther U. Interleukin-6 is necessary, but not sufficient, for induction of the humanC-reactive protein gene in vivo. Biochemical Journal [Internet]. 1997 ago 1;325(3):617-621. Disponible en: http://doi.org/10.1042/bj3250617
Calabro P, Willerson JT, Yeh ETH. Inflammatory Cytokines Stimulated C-Reactive Protein Production by Human Coronary Artery Smooth Muscle Cells. Circulation [Internet]. 2003 oct 21;108(16):1930-1932. Disponible en: https://doi.org/10.1161/01.cir.0000096055.62724.c5
Badimon L, Peña E, Arderiu G, Padró T, Slevin M, Vilahur G, Chiva-Blanch G. C-Reactive Protein in Atherothrombosis and Angiogenesis. Frontiers In Immunology [Internet]. 2018 mar 2;9. Disponible en: https://doi.org/10.3389/fimmu.2018.00430
Molins B, PeñA E, Vilahur G, Mendieta C, Slevin M, Badimon L. C-Reactive Protein Isoforms Differ in Their Effects on Thrombus Growth. Arteriosclerosis Thrombosis and Vascular Biology [Internet]. 2008 sep 12;28(12):2239-2246. Disponible en: https://doi.org/10.1161/atvbaha.108.174359
Gaziano TA, Abrahams-Gessel S, Gomez-Olive FX, Wade A, Crowther NJ, Alam S, Manne-Goehler J, Kabudula CW, Wagner R, Rohr J, Montana L, Kahn K, Bärnighausen TW, Berkman LF, Tollman S. Cardiometabolic risk in a population of older adults with multiple co-morbidities in rural south africa: the HAALSI (Health and Aging in Africa: longitudinal studies of INDEPTH communities) study. BMC Public Health [Internet]. 2017 feb 17;17(1). Disponible en: https://doi.org/10.1186/s12889-017-4117-y
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-SinDerivadas 4.0.
Derechos de autor 2025 En caso de que el manuscrito sea aprobado para su publicación, los autores conservan los derechos de autor y ceden a la revista el derecho de la primera publicación y de que pueda editarlo, reproducirlo, exhibirlo y comunicarlo en el país y en el extranjero mediante medios impresos y electrónicos.