Monocyte distribution width alterations and cytokine storm are modulated by circulating histones.
COVID-19
cytokine
histones
monocyte
monocyte distribution width
sepsis
Journal
Clinical chemistry and laboratory medicine
ISSN: 1437-4331
Titre abrégé: Clin Chem Lab Med
Pays: Germany
ID NLM: 9806306
Informations de publication
Date de publication:
26 07 2023
26 07 2023
Historique:
received:
26
01
2023
accepted:
17
02
2023
medline:
3
7
2023
pubmed:
28
2
2023
entrez:
27
2
2023
Statut:
epublish
Résumé
Extracellular histone levels are associated with the severity of many human pathologies, including sepsis and COVID-19. This study aimed to investigate the role of extracellular histones on monocyte distribution width (MDW), and their effect on the release of cytokines by blood cells. Peripheral venous blood was collected from healthy subjects and treated with different doses of a histone mixture (range 0-200 μg/mL) to analyze MDW modifications up-to 3 h and digital microscopy of blood smears. Plasma obtained after 3 h of histone treatment were assayed to evaluate a panel of 24 inflammatory cytokines. MDW values significantly increased in a time- and dose-dependent manner. These findings are associated with the histone-induced modifications of cell volume, cytoplasmic granularity, vacuolization, and nuclear structure of monocytes, promoting their heterogeneity without affecting their count. After 3 h of treatment almost all cytokines significantly increased in a dose-dependent manner. The most relevant response was shown by the significantly increased G-CSF levels, and by the increase of IL-1β, IL-6, MIP-1β, and IL-8 at the histone doses of 50, 100, and 200 µg/mL. VEGF, IP-10, GM-CSF, TNF-α, Eotaxin, and IL-2 were also up-regulated, and a lower but significant increase was observed for IL-15, IL-5, IL-17, bFGF, IL-10, IFN-γ, MCP-1, and IL-9. Circulating histones critically induce functional alterations of monocytes mirrored by MDW, monocyte anisocytosis, and hyperinflammation/cytokine storm in sepsis and COVID-19. MDW and circulating histones may be useful tools to predict higher risks of worst outcomes.
Identifiants
pubmed: 36847604
pii: cclm-2023-0093
doi: 10.1515/cclm-2023-0093
doi:
Substances chimiques
Histones
0
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1525-1535Informations de copyright
© 2023 the author(s), published by De Gruyter, Berlin/Boston.
Références
Chen, R, Kang, R, Fan, XG, Tang, D. Release and activity of histone in diseases. Cell Death Dis 2014;5:e1370. https://doi.org/10.1038/cddis.2014.337 .
doi: 10.1038/cddis.2014.337
Szatmary, P, Huang, W, Criddle, D, Tepikin, A, Sutton, R. Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders. J Cell Mol Med 2018;22:4617–29. https://doi.org/10.1111/jcmm.13797 .
doi: 10.1111/jcmm.13797
Silk, E, Zhao, H, Weng, H, Ma, D. The role of extracellular histone in organ injury. Cell Death Dis 2017;8:e2812. https://doi.org/10.1038/cddis.2017.52 .
doi: 10.1038/cddis.2017.52
Zhang, X, Li, X. The role of histones and heparin in sepsis: a review. J Intensive Care Med 2022;37:319–26. https://doi.org/10.1177/0885066621992320 .
doi: 10.1177/0885066621992320
Ligi, D, Giglio, RV, Henry, BM, Lippi, G, Ciaccio, M, Plebani, M, et al.. What is the impact of circulating histones in COVID-19: a systematic review. Clin Chem Lab Med 2022;60:1506–17. https://doi.org/10.1515/cclm-2022-0574 .
doi: 10.1515/cclm-2022-0574
Ligi, D, Maniscalco, R, Plebani, M, Lippi, G, Mannello, F. Do circulating histones represent the missing link among COVID-19 infection and multiorgan injuries, microvascular coagulopathy and systemic hyperinflammation? J Clin Med 2022;11:1800. https://doi.org/10.3390/jcm11071800 .
doi: 10.3390/jcm11071800
Ekaney, ML, Otto, GP, Sossdorf, M, Sponholz, C, Boehringer, M, Loesche, W, et al.. Impact of plasma histones in human sepsis and their contribution to cellular injury and inflammation. Crit Care 2014;18:543. https://doi.org/10.1186/s13054-014-0543-8 .
doi: 10.1186/s13054-014-0543-8
Shaw, RJ, Abrams, ST, Austin, J, Taylor, JM, Lane, S, Dutt, T, et al.. Circulating histones play a central role in COVID-19-associated coagulopathy and mortality. Haematologica 2021;106:2493–8. https://doi.org/10.3324/haematol.2021.278492 .
doi: 10.3324/haematol.2021.278492
Cani, E, Dwivedi, DJ, Liaw, KL, Fraser, DD, Yeh, CH, Martin, C, et al.. Immunothrombosis biomarkers for distinguishing coronavirus disease 2019 patients from noncoronavirus disease septic patients with pneumonia and for predicting ICU mortality. Crit Care Explor 2021;3:e0588. https://doi.org/10.1097/cce.0000000000000588 .
doi: 10.1097/cce.0000000000000588
Gallo, CG, Fiorino, S, Posabella, G, Antonacci, D, Tropeano, A, Pausini, E, et al.. COVID-19, what could sepsis, severe acute pancreatitis, gender differences, and aging teach us? Cytokine 2021;148:155628. https://doi.org/10.1016/j.cyto.2021.155628 .
doi: 10.1016/j.cyto.2021.155628
Riva, G, Castellano, S, Nasillo, V, Ottomano, AM, Bergonzini, G, Paolini, A, et al.. Monocyte Distribution Width (MDW) as novel inflammatory marker with prognostic significance in COVID-19 patients. Sci Rep 2021;11:12716. https://doi.org/10.1038/s41598-021-92236-6 .
doi: 10.1038/s41598-021-92236-6
Agnello, L, Vidali, M, Lo Sasso, B, Giglio, RV, Gambino, CM, Scazzone, C, et al.. Monocyte distribution width (MDW) as a screening tool for early detecting sepsis: a systematic review and meta-analysis. Clin Chem Lab Med 2022;60:786–92. https://doi.org/10.1515/cclm-2021-1331 .
doi: 10.1515/cclm-2021-1331
Alsuwaidi, L, Al Heialy, S, Shaikh, N, Al Najjar, F, Seliem, R, Han, A, et al.. Monocyte distribution width as a novel sepsis indicator in COVID-19 patients. BMC Infect Dis 2022;22:27. https://doi.org/10.1186/s12879-021-07016-4 .
doi: 10.1186/s12879-021-07016-4
Lorubbio, M, Tacconi, D, Iannelli, G, Feri, M, Scala, R, Montemerani, S, et al.. The role of monocyte distribution width (MDW) in the prognosis and monitoring of COVID-19 patients. Clin Biochem 2022;103:29–31. https://doi.org/10.1016/j.clinbiochem.2022.02.007 .
doi: 10.1016/j.clinbiochem.2022.02.007
Ognibene, A, Lorubbio, M, Magliocca, P, Tripodo, E, Vaggelli, G, Iannelli, G, et al.. Elevated monocyte distribution width in COVID-19 patients: the contribution of the novel sepsis indicator. Clin Chim Acta 2020;509:22–4. https://doi.org/10.1016/j.cca.2020.06.002 .
doi: 10.1016/j.cca.2020.06.002
Polilli, E, Sozio, F, Frattari, A, Persichitti, L, Sensi, M, Posata, R, et al.. Comparison of monocyte distribution width (MDW) and procalcitonin for early recognition of sepsis. PLoS One 2020;15:e0227300. https://doi.org/10.1371/journal.pone.0227300 .
doi: 10.1371/journal.pone.0227300
Hossain, R, Ayub, S, Tarabichi, Y. Monocyte distribution width adds prognostic value in detection of COVID-19 respiratory failure. Int J Lit Humanit 2022;44:e64–e6. https://doi.org/10.1111/ijlh.13712 .
doi: 10.1111/ijlh.13712
Lippi, G, Sanchis-Gomar, F, Henry, BM. Pooled analysis of monocyte distribution width in subjects with SARS-CoV-2 infection. Int J Lit Humanit 2021;43:O161–O3. https://doi.org/10.1111/ijlh.13482 .
doi: 10.1111/ijlh.13482
Zeng, F, Huang, Y, Guo, Y, Yin, M, Chen, X, Xiao, L, et al.. Association of inflammatory markers with the severity of COVID-19: a meta-analysis. Int J Infect Dis 2020;96:467–74. https://doi.org/10.1016/j.ijid.2020.05.055 .
doi: 10.1016/j.ijid.2020.05.055
Ligi, D, Lo Sasso, B, Giglio, RV, Maniscalco, R, DellaFranca, C, Agnello, L, et al.. Circulating histones contribute to monocyte and MDW alterations as common mediators in classical and COVID-19 sepsis. Crit Care 2022;26:260. https://doi.org/10.1186/s13054-022-04138-2 .
doi: 10.1186/s13054-022-04138-2
Crouser, ED, Parrillo, JE, Seymour, C, Angus, DC, Bicking, K, Tejidor, L, et al.. Improved early detection of sepsis in the ED with a novel monocyte distribution width biomarker. Chest 2017;152:518–26. https://doi.org/10.1016/j.chest.2017.05.039 .
doi: 10.1016/j.chest.2017.05.039
Radzyukevich, YV, Kosyakova, NI, Prokhorenko, IR. Participation of monocyte subpopulations in progression of experimental endotoxemia (EE) and systemic inflammation. J Immunol Res 2021;2021:1762584. https://doi.org/10.1155/2021/1762584 .
doi: 10.1155/2021/1762584
Ahmadi, E, Bagherpour, Z, Zarei, E, Omidkhoda, A. Pathological effects of SARS-CoV-2 on hematological and immunological cells: alterations in count, morphology, and function. Pathol Res Pract 2022;231:153782. https://doi.org/10.1016/j.prp.2022.153782 .
doi: 10.1016/j.prp.2022.153782
Merad, M, Martin, JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol 2020;20:355–62. https://doi.org/10.1038/s41577-020-0331-4 .
doi: 10.1038/s41577-020-0331-4
Zini, G, Bellesi, S, Ramundo, F, d’Onofrio, G. Morphological anomalies of circulating blood cells in COVID-19. Am J Hematol 2020;95:870–2. https://doi.org/10.1002/ajh.25824 .
doi: 10.1002/ajh.25824
Ligi, D, Sasso, BL, Henry, BM, Ciaccio, M, Lippi, G, Plebani, M, et al.. Deciphering the role of monocyte and monocyte distribution width (MDW) in COVID-19: an updated systematic review and meta-analysis. Clin Chem Lab Med 2023;61:960–73. https://doi.org/10.1515/cclm-2022-0936 .
doi: 10.1515/cclm-2022-0936
Agnello, L, Bivona, G, Vidali, M, Scazzone, C, Giglio, RV, Iacolino, G, et al.. Monocyte distribution width (MDW) as a screening tool for sepsis in the Emergency Department. Clin Chem Lab Med 2020;58:1951–7. https://doi.org/10.1515/cclm-2020-0417 .
doi: 10.1515/cclm-2020-0417
Agnello, L, Lo Sasso, B, Bivona, G, Gambino, CM, Giglio, RV, Iacolino, G, et al.. Reference interval of monocyte distribution width (MDW) in healthy blood donors. Clin Chim Acta 2020;510:272–7. https://doi.org/10.1016/j.cca.2020.07.036 .
doi: 10.1016/j.cca.2020.07.036
Singh, A, Verma, S, Modak, SB, Chaturvedi, MM, Purohit, JS. Extra-nuclear histones: origin, significance and perspectives. Mol Cell Biochem 2022;477:507–24. https://doi.org/10.1007/s11010-021-04300-4 .
doi: 10.1007/s11010-021-04300-4
Damsgaard, CT, Lauritzen, L, Calder, PC, Kjaer, TM, Frøkiaer, H. Whole-blood culture is a valid low-cost method to measure monocytic cytokines - a comparison of cytokine production in cultures of human whole-blood, mononuclear cells and monocytes. J Immunol Methods 2009;340:95–101. https://doi.org/10.1016/j.jim.2008.10.005 .
doi: 10.1016/j.jim.2008.10.005
Chousterman, BG, Swirski, FK, Weber, GF. Cytokine storm and sepsis disease pathogenesis. Semin Immunopathol 2017;39:517–28. https://doi.org/10.1007/s00281-017-0639-8 .
doi: 10.1007/s00281-017-0639-8
Liao, M, Liu, Y, Yuan, J, Wen, Y, Xu, G, Zhao, J, et al.. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med 2020;26:842–4. https://doi.org/10.1038/s41591-020-0901-9 .
doi: 10.1038/s41591-020-0901-9
Zhang, Q, Bastard, P, Liu, Z, Le Pen, J, Moncada-Velez, M, Chen, J, et al.. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 2020;370:eabd4570. https://doi.org/10.1126/science.abd4570 .
doi: 10.1126/science.abd4570
Zhou, Z, Ren, L, Zhang, L, Zhong, J, Xiao, Y, Jia, Z, et al.. Heightened innate immune responses in the respiratory tract of COVID-19 patients. Cell Host Microbe 2020;27:883–90.e2. https://doi.org/10.1016/j.chom.2020.04.017 .
doi: 10.1016/j.chom.2020.04.017
Eichhorn, T, Linsberger, I, Lauková, L, Tripisciano, C, Fendl, B, Weiss, R, et al.. Analysis of inflammatory mediator profiles in sepsis patients reveals that extracellular histones are strongly elevated in nonsurvivors. Mediat Inflamm 2021;2021:8395048. https://doi.org/10.1155/2021/8395048 .
doi: 10.1155/2021/8395048
Mera, S, Tatulescu, D, Cismaru, C, Bondor, C, Slavcovici, A, Zanc, V, et al.. Multiplex cytokine profiling in patients with sepsis. Apmis 2011;119:155–63. https://doi.org/10.1111/j.1600-0463.2010.02705.x .
doi: 10.1111/j.1600-0463.2010.02705.x
Gouel-Chéron, A, Allaouchiche, B, Guignant, C, Davin, F, Floccard, B, Monneret, G. Early interleukin-6 and slope of monocyte human leukocyte antigen-DR: a powerful association to predict the development of sepsis after major trauma. PLoS One 2012;7:e33095. https://doi.org/10.1371/journal.pone.0033095 .
doi: 10.1371/journal.pone.0033095
Wu, HP, Chen, CK, Chung, K, Tseng, JC, Hua, CC, Liu, YC, et al.. Serial cytokine levels in patients with severe sepsis. Inflamm Res 2009;58:385–93. https://doi.org/10.1007/s00011-009-0003-0 .
doi: 10.1007/s00011-009-0003-0
Kellum, JA, Kong, L, Fink, MP, Weissfeld, LA, Yealy, DM, Pinsky, MR, et al.. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the genetic and inflammatory markers of sepsis (GenIMS) study. Arch Intern Med 2007;167:1655–63. https://doi.org/10.1001/archinte.167.15.1655 .
doi: 10.1001/archinte.167.15.1655
Hirano, T, Murakami, M. COVID-19: a new virus, but a familiar receptor and cytokine release syndrome. Immunity 2020;52:731–3. https://doi.org/10.1016/j.immuni.2020.04.003 .
doi: 10.1016/j.immuni.2020.04.003
Liu, Y, Zhang, C, Huang, F, Yang, Y, Wang, F, Yuan, J, et al.. Elevated plasma levels of selective cytokines in COVID-19 patients reflect viral load and lung injury. Natl Sci Rev 2020;7:1003–11. https://doi.org/10.1093/nsr/nwaa037 .
doi: 10.1093/nsr/nwaa037
Liu, J, Li, S, Liu, J, Liang, B, Wang, X, Wang, H, et al.. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020;55:102763. https://doi.org/10.1016/j.ebiom.2020.102763 .
doi: 10.1016/j.ebiom.2020.102763
Mohammad, RA. Use of granulocyte colony-stimulating factor in patients with severe sepsis or septic shock. Am J Health Syst Pharm 2010;67:1238–45. https://doi.org/10.2146/ajhp090325 .
doi: 10.2146/ajhp090325
Xu, J, Zhang, X, Monestier, M, Esmon, NL, Esmon, CT. Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury. J Immunol 2011;187:2626–31. https://doi.org/10.4049/jimmunol.1003930 .
doi: 10.4049/jimmunol.1003930
Allam, R, Kumar, SV, Darisipudi, MN, Anders, HJ. Extracellular histones in tissue injury and inflammation. J Mol Med 2014;92:465–72. https://doi.org/10.1007/s00109-014-1148-z .
doi: 10.1007/s00109-014-1148-z
Hogwood, J, Pitchford, S, Mulloy, B, Page, C, Gray, E. Heparin and non-anticoagulant heparin attenuate histone-induced inflammatory responses in whole blood. PLoS One 2020;15:e0233644. https://doi.org/10.1371/journal.pone.0233644 .
doi: 10.1371/journal.pone.0233644
Kawai, C, Kotani, H, Miyao, M, Ishida, T, Jemail, L, Abiru, H, et al.. Circulating extracellular histones are clinically relevant mediators of multiple organ injury. Am J Pathol 2016;186:829–43. https://doi.org/10.1016/j.ajpath.2015.11.025 .
doi: 10.1016/j.ajpath.2015.11.025
Moiana, M, Aranda, F, de Larranaga, G. A focus on the roles of histones in health and diseases. Clin Biochem 2021;94:12–9. https://doi.org/10.1016/j.clinbiochem.2021.04.019 .
doi: 10.1016/j.clinbiochem.2021.04.019
Westman, J, Papareddy, P, Dahlgren, MW, Chakrakodi, B, Norrby-Teglund, A, Smeds, E, et al.. Extracellular histones induce chemokine production in whole blood ex vivo and leukocyte recruitment in vivo. PLoS Pathog 2015;11:e1005319. https://doi.org/10.1371/journal.ppat.1005319 .
doi: 10.1371/journal.ppat.1005319
Sharma, N, Haggstrom, L, Sohrabipour, S, Dwivedi, DJ, Liaw, PC. Investigations of the effectiveness of heparin variants as inhibitors of histones. J Thromb Haemostasis 2022;20:1485–95. https://doi.org/10.1111/jth.15706 .
doi: 10.1111/jth.15706