The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
Extracellular hemin crisis triggers acute chest syndrome in sickle mice
Open accessAbstract
The prevention and treatment of acute chest syndrome (ACS) is a major clinical concern in sickle cell disease (SCD).However, the mechanism underlying the pathogenesis of ACS remains elusive.We tested the hypothesis that the hemolysis byproduct hemin elicits events that induce ACS.Infusion of a low dose of hemin caused acute intravascular hemolysis and autoamplification of extracellular hemin in transgenic sickle mice, but not in sickle-trait littermates.The sickle mice developed multiple symptoms typical of ACS and succumbed rapidly.Pharmacologic inhibition of TLR4 and hemopexin replacement therapy prior to hemin infusion protected sickle mice from developing ACS.Replication of the ACS-like phenotype in nonsickle mice revealed that the mechanism of lung injury due to extracellular hemin is independent of SCD.Using genetic and bone marrow chimeric tools, we confirmed that TLR4 expressed in nonhematopoietic vascular tissues mediated this lethal type of acute lung injury.Respiratory failure was averted after the onset of ACS-like symptoms in sickle mice by treating them with recombinant hemopexin.Our results reveal a mechanism that helps to explain the pathogenesis of ACS, and we provide proof of principle for therapeutic strategies to prevent and treat this condition in mice. Results Extracellular hemin elevation causes a lethal hemolytic crisis in sickle mice.To mimic acute extracellular hemin release, transgenic Townes sickle mice (referred to herein as SS mice; see Methods) and control sickletrait (AS) and wild-type human Hb (AA) mice were infused with a relatively low dose of purified hemin (35 μmol/kg).No adverse effects were seen in the control mice, but a majority of SS mice developed labored breathing and died within 2 hours (Figure 1A).We confirmed these acute adverse effects in a second murine model of SCD (Berkeley sickle mice; see Methods) and showed that the lethality rate was dependent on the dose of hemin (Figure 1B).A previous study had shown that 40 μmol/kg hemin given i.p. did not cause any fatalities in the Berkeley sickle mouse (26).A higher dose (70 μmol/kg) given i.v. had no adverse effects in wild-type mice (17, 27); moreover, the SS mouse deaths occurred 24 hours before hepatic failure onset, due to hemin overload in septic mice (28).Thus, our results in the SS mice revealed an unusual effect of extracellular hemin that had not previously been described.Plasma hemopexin (Hx) levels decreased sharply in all animals, coincident with nearly 50% clearance of the hemin bolus within Conflict of interest: The authors have declared that no conflict of interest exists.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“animal models showing that heme is directly responsible for acute lung injury in SCD mouse models (89).”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [89]
The cited source says what the claim attributes to it.
In the citing paper
“high levels of hemopexin, the enzyme that scavenges heme, can rescue acute lung injury (89), while HO-1 deficiency potentiates it (57).”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [89]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mortality in sickle cell disease. Life expectancy and risk factors for early death
Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., & Klug, P. P. (1994) · New England Journal of Medicine · doi:10.1056/nejm199406093302303 · Cited by 3,320 · cited 1×
“Acute chest syndrome (ACS) is the second most common reason for hospital admission of SCD patients (2) and the leading cause of referral to intensive care units (3), and it is associated with a high mortality rate (4).”
Animal models of acute lung injury
Matute‐Bello, G., Frevert, C. W., & Martin, T. R. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00010.2008 · Cited by 1,762
Endotoxin-tolerant Mice Have Mutations in Toll-like Receptor 4 ( Tlr4 )
Qureshi, S. T., Larivière, L., Leveque, G., Clermont, S., Moore, K. J., Gros, P., & Malo, D. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.4.615 · Cited by 1,532
Causes and Outcomes of the Acute Chest Syndrome in Sickle Cell Disease
Vichinsky, E. P., Neumayr, L. D., Earles, A. N., Williams, R., Lennette, E. T., Dean, D., Nickerson, B., Orringer, E., McKie, V., Bellevue, R., et al. (2000) · New England Journal of Medicine · doi:10.1056/nejm200006223422502 · Cited by 1,234
Opal, S. M., Laterre, P.-F., Francois, B., LaRosa, S. P., Angus, D. C., Mira, J.-P., Wittebole, X., Dugernier, T., Perrotin, D., Tidswell, M., et al. (2013) · JAMA · doi:10.1001/jama.2013.2194 · Cited by 812
Castro, O. L., Brambilla, D. J., Thorington, B. D., Reindorf, C. A., Scott, R., GILLETTE, P. N., Vera, J., & Levy, P. S. (1994) · Blood · doi:10.1182/blood.v84.2.643.643 · Cited by 805
Pro-oxidant and cytotoxic effects of circulating heme
Jeney, V., Balla, J., Yachie, A., Varga, Z., Vercellotti, G. M., Eaton, J. W., & Balla, G. (2002) · Blood · doi:10.1182/blood.v100.3.879 · Cited by 633
Castro, O. L., Brambilla, D. J., Thorington, B. D., et al. (1994) · Blood · doi:10.1182/blood.v84.2.643.bloodjournal842643 · Cited by 615
Characterization of Heme as Activator of Toll-like Receptor 4
Figueiredo, R. T., Fernandez, P. L., Mourao-Sa, D. S., Porto, B. N., Dutra, F. F., Alves, L. S., Oliveira, M. F., Oliveira, P. L., Graça-Souza, A. V., & Bozza, M. T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610737200 · Cited by 576
Hemmi, H., Takeuchi, O., Sato, S., Yamamoto, M., Kaisho, T., Sanjo, H., Kawai, T., Hoshino, K., Takeda, K., & Akira, S. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040520 · Cited by 576
Flagged first, then by citations
Research works printed but not linked: 1
- Sprinkle, 1986, Am J Pediatr Hematol Oncol., 8, 105
Cited by
Sorted by citations
Pathophysiology of Sickle Cell Disease
Sundd, P., Gladwin, M. T., & Novelli, E. M. (2019) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012838 · Cited by 813
Intravascular hemolysis and the pathophysiology of sickle cell disease
Kato, G. J., Steinberg, M. H., & Gladwin, M. T. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89741 · Cited by 748
Belcher, J. D., Chen, C., Nguyen, J., Milbauer, L., Abdulla, F., Alayash, A. I., Smith, A., Nath, K. A., Hebbel, R. P., & Vercellotti, G. M. (2014) · Blood · doi:10.1182/blood-2013-04-495887 · Cited by 695
Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia
Kuhn, V., Diederich, L., Keller, T. C. S., Kramer, C. M., Lückstädt, W., Panknin, C., Suvorava, T., Isakson, B. E., Kelm, M., & Cortese-Krott, M. M. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6954 · Cited by 469
Zhang, D., Xu, C., Manwani, D., & Frenette, P. S. (2016) · Blood · doi:10.1182/blood-2015-09-618538 · Cited by 413
Heme on innate immunity and inflammation
Dutra, F. F., & Bozza, M. T. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00115 · Cited by 370
Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease
Chen, G., Zhang, D., Fuchs, T. A., Manwani, D., Wagner, D. D., & Frenette, P. S. (2014) · Blood · doi:10.1182/blood-2013-10-529982 · Cited by 354
Hemolysis-induced lethality involves inflammasome activation by heme
Dutra, F. F., Alves, L. S., Rodrigues, D., Fernandez, P. L., de Oliveira, R. B., Golenbock, D. T., Zamboni, D. S., & Bozza, M. T. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405023111 · Cited by 353
Inflammation in sickle cell disease
Conran, N., & Belcher, J. D. (2018) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-189012 · Cited by 316
Vinchi, F., Costa da Silva, M., Ingoglia, G., Petrillo, S., Brinkman, N., Zuercher, A., Cerwenka, A., Tolosano, E., & Muckenthaler, M. U. (2016) · Blood · doi:10.1182/blood-2015-08-663245 · Cited by 269
Schaer, D. J., Vinchi, F., Ingoglia, G., Tolosano, E., & Buehler, P. W. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00415 · Cited by 281
Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders
Smith, A., & McCulloh, R. J. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00187 · Cited by 258
Camus, S. M., Moraes, J. A., Bonnin, P., Abbyad, P., Jeune, S. L., Lionnet, F., Loufrani, L., Grimaud, L., Lambry, J., Charue, D., et al. (2015) · Blood · doi:10.1182/blood-2014-07-589283 · Cited by 266
Pro-inflammatory Actions of Heme and Other Hemoglobin-Derived DAMPs
Bozza, M. T., & Jeney, V. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01323 · Cited by 214
Heme dynamics and trafficking factors revealed by genetically encoded fluorescent heme sensors
Hanna, D. A., Harvey, R. M., Martinez-Guzman, O., Yuan, X., Chandrasekharan, B. P., Raju, G., Outten, F. W., Hamza, I., & Reddi, A. R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1523802113 · Cited by 191
The Red Blood Cell—Inflammation Vicious Circle in Sickle Cell Disease
Nader, É., Romana, M., & Connes, P. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00454 · Cited by 207
Qiu, Y., Ahn, B., Sakurai, Y., Hansen, C. E., Tran, R., Mimche, P. N., Mannino, R. G., Ciciliano, J. C., Lamb, T. J., Joiner, C. H., et al. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0224-z · Cited by 192
Self-citationChaturvedi, S., & DeBaun, M. R. (2015) · American Journal of Hematology · doi:10.1002/ajh.24235 · Cited by 200
Therapeutic strategies for sickle cell disease: towards a multi-agent approach
Telen, M. J., Malik, P., & Vercellotti, G. M. (2018) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0003-2 · Cited by 188
Pathophysiology and treatment of pulmonary hypertension in sickle cell disease
Gordeuk, V. R., Castro, O. L., & Machado, R. F. (2016) · Blood · doi:10.1182/blood-2015-08-618561 · Cited by 184
Deuel, J., Schaer, C. A., Boretti, F. S., Opitz, L., García‐Rubio, I., Baek, J. H., Spahn, D. R., Buehler, P. W., & Schaer, D. J. (2016) · Cell Death and Disease · doi:10.1038/cddis.2015.392 · Cited by 179
Atherogenesis and iron: from epidemiology to cellular level
Vinchi, F., Muckenthaler, M. U., da Silva, M. C., Balla, G. J., Balla, J., & Jeney, V. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00094 · Cited by 176
Acute Chest Syndrome in Children with Sickle Cell Disease
Jain, S., Bakshi, N., & Krishnamurti, L. (2017) · Pediatric Allergy Immunology and Pulmonology · doi:10.1089/ped.2017.0814 · Cited by 170
Hemolysis, free hemoglobin toxicity, and scavenger protein therapeutics
Vallelian, F., Buehler, P. W., & Schaer, D. J. (2022) · Blood · doi:10.1182/blood.2022015596 · Cited by 173
Novelli, E. M., & Gladwin, M. T. (2015) · CHEST Journal · doi:10.1016/j.chest.2015.12.016 · Cited by 166
Cardiovascular complications and risk of death in sickle-cell disease
Gladwin, M. T. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00647-4 · Cited by 164
Red cell DAMPs and inflammation
Mendonça, R., Silveira, A. A. A., & Conran, N. (2016) · Inflammation Research · doi:10.1007/s00011-016-0955-9 · Cited by 163
Red alert: labile heme is an alarmin
Soares, M. P., & Bozza, M. T. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.11.006 · Cited by 148
Heme: Modulator of Plasma Systems in Hemolytic Diseases
Roumenina, L. T., Rayes, J., Lacroix‐Desmazes, S., & Dimitrov, J. D. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.01.004 · Cited by 149
Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli
Bennewitz, M. F., Jimenez, M. A., Vats, R., Tutuncuoglu, E., Jonassaint, J., Kato, G. J., Gladwin, M. T., & Sundd, P. (2017) · JCI Insight · doi:10.1172/jci.insight.89761 · Cited by 139
Vasculopathy and pulmonary hypertension in sickle cell disease
Potoka, K. P., & Gladwin, M. T. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00252.2014 · Cited by 135
The impact of xanthine oxidase (XO) on hemolytic diseases
Schmidt, H. M., Kelley, E. E., & Straub, A. C. (2018) · Redox Biology · doi:10.1016/j.redox.2018.101072 · Cited by 133
Heme as a Target for Therapeutic Interventions
Immenschuh, S., Vijayan, V., Janciauskiene, S. M., & Gueler, F. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00146 · Cited by 130
Belcher, J. D., Chen, C., Nguyen, J., Zhang, P., Abdulla, F. A., Nguyen, P., Killeen, T. F., Xu, P. C., O'Sullivan, G., Nath, K. A., et al. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6571 · Cited by 114
Belcher, J. D., Chen, C., Nguyen, J., Abdulla, F. A., Zhang, P., Nguyen, H. V., Nguyen, P., Killeen, T. F., Miescher, S., Brinkman, N. J., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0196455 · Cited by 116
The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease
Gbotosho, O. T., Kapetanaki, M. G., & Kato, G. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.561917 · Cited by 118
Erythroid DAMPs drive inflammation in SCD
Gladwin, M. T., & Ofori-Acquah, S. F. (2014) · Blood · doi:10.1182/blood-2014-03-563874 · Cited by 113
Self-citationRole of Heme in Cardiovascular Physiology and Disease
Sawicki, K. T., Chang, H., & Ardehali, H. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.114.001138 · Cited by 112
Iron, Inflammation, and Early Death in Adults With Sickle Cell Disease
van Beers, E. J., Yang, Y., Raghavachari, N., Tian, X., Allen, D. T., Nichols, J. S., Mendelsohn, L. G., Nekhai, S. A., Gordeuk, V. R., Taylor, J. G., et al. (2014) · Circulation Research · doi:10.1161/circresaha.116.304577 · Cited by 100
The Development and Consequences of Red Blood Cell Alloimmunization
Arthur, C. M., & Stowell, S. R. (2022) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-042320-110411 · Cited by 97
Cell-free hemoglobin: a novel mediator of acute lung injury
Shaver, C. M., Upchurch, C. P., Janz, D. R., Grove, B. S., Putz, N. D., Wickersham, N. E., Dikalov, S., Ware, L. B., & Bastarache, J. A. (2016) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00155.2015 · Cited by 97
Hemolysis Derived Products Toxicity and Endothelium: Model of the Second Hit
Frimat, M., Boudhabhay, I., & Roumenina, L. T. (2019) · Toxins · doi:10.3390/toxins11110660 · Cited by 99
Vats, R., Brzóska, T., Bennewitz, M. F., Jimenez, M. A., Pradhan‐Sundd, T., Tütüncüoğlu, E., Jonassaint, J., Gutierrez, E., Watkins, S. C., Shiva, S., et al. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201807-1370oc · Cited by 99
Wang, Q., & Zennadi, R. (2021) · Antioxidants · doi:10.3390/antiox10101608 · Cited by 103
Protein aggregation as a cellular response to oxidative stress induced by heme and iron
Vasconcellos, L. R. C., Dutra, F. F., Siqueira, M. S., Paula-Neto, H. A., Dahan, J., Souza, E. K., Carneiro, L. A. M., Bozza, M. T., & Travassos, L. H. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1608928113 · Cited by 89
Haptoglobin Therapeutics and Compartmentalization of Cell-Free Hemoglobin Toxicity
Buehler, P. W., Humar, R., & Schaer, D. J. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.02.004 · Cited by 90
Heme Catabolic Pathway in Inflammation and Immune Disorders
Wu, B., Wu, Y., & Tang, W. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00825 · Cited by 90
Excess of heme induces tissue factor-dependent activation of coagulation in mice
Sparkenbaugh, E., Chantrathammachart, P., Wang, S., Jonas, W., Kirchhofer, D., Gailani, D., Gruber, A., Kasthuri, R. S., Key, N. S., Mackman, N., et al. (2015) · Haematologica · doi:10.3324/haematol.2014.114728 · Cited by 85
Hemolysis transforms liver macrophages into antiinflammatory erythrophagocytes
Pfefferlé, M., Ingoglia, G., Schaer, C. A., Yalamanoglu, A., Buzzi, R. M., Dubach, I. L., Tan, G., López-Cano, E. Y., Schulthess, N., Hansen, K., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci137282 · Cited by 78
Characterization of plasma labile heme in hemolytic conditions
Gouveia, Z., Carlos, A. R., Yuan, X., Aires‐da‐Silva, F., Stocker, R., Maghzal, G. J., Leal, S. S., Gomes, C. M., Todorovic, S., Iranzo, O., et al. (2017) · The FEBS Journal · doi:10.1111/febs.14192 · Cited by 70
Chonat, S., Quarmyne, M., Bennett, C. M., Dean, C. L., Joiner, C. H., Fasano, R. M., & Stowell, S. R. (2018) · Haematologica · doi:10.3324/haematol.2018.194670 · Cited by 73
Innate immune cells, major protagonists of sickle cell disease pathophysiology
Allali, S., Maciel, T. T., Hermine, O., & de Montalembert, M. (2020) · Haematologica · doi:10.3324/haematol.2019.229989 · Cited by 79
Basic Mechanisms of Hemolysis-Associated Thrombo-Inflammation and Immune Dysregulation
Dimitrov, J. D., Roumenina, L. T., Perrella, G., & Rayes, J. (2023) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.123.318780 · Cited by 75
Proteasome inhibition and oxidative reactions disrupt cellular homeostasis during heme stress
Vallelian, F., Deuel, J. W., Opitz, L., Schaer, C. A., Puglia, M., Lönn, M., Engelsberger, W., Schauer, S., Karnaukhova, E., Spahn, D. R., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.154 · Cited by 66
Jana, S., Strader, M. B., Meng, F., Hicks, W. A., Kassa, T., Tarandovskiy, I. D., Paoli, S. D., Šimák, J., Heaven, M. R., Belcher, J. D., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.120451 · Cited by 70
Haematological determinants of cardiac involvement in adults with sickle cell disease
Damy, T., Bodez, D., Habibi, A., Guellich, A., Rappeneau, S., Inamo, J., Guendouz, S., Gellen-Dautremer, J., Pissard, S., Loric, S., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehv555 · Cited by 65
Vats, R., Kaminski, T. W., Brzóska, T., Leech, J. A., Tütüncüoğlu, E., Katoch, O., Jonassaint, J., Tejero, J., Novelli, E. M., Pradhan‐Sundd, T., et al. (2022) · Blood · doi:10.1182/blood.2021014552 · Cited by 65
Oh, J., Hamm, J. D., Xu, X., Genschmer, K. R., Zhong, M., Lebensburger, J. D., Marques, M. B., Kerby, J. D., Pittet, J., Gaggar, A., et al. (2016) · Redox Biology · doi:10.1016/j.redox.2016.08.003 · Cited by 66
Revisiting the putative role of heme as a trigger of inflammation
Vallelian, F., Schaer, C. A., Deuel, J., Ingoglia, G., Humar, R., Buehler, P. W., & Schaer, D. J. (2018) · Pharmacology Research & Perspectives · doi:10.1002/prp2.392 · Cited by 63
Critical role of C5a in sickle cell disease
Vercellotti, G. M., Dalmasso, A. P., Schaid, T. R., Nguyen, J., Chen, C., Ericson, M. E., Abdulla, F. A., Killeen, T. F., Lindorfer, M. A., Taylor, R. P., et al. (2018) · American Journal of Hematology · doi:10.1002/ajh.25384 · Cited by 64
Oxidative pathways in the sickle cell and beyond
Alayash, A. I. (2017) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2017.05.009 · Cited by 63
Sickle cell disease increases high mobility group box 1: a novel mechanism of inflammation
Xu, H., Wandersee, N. J., Guo, Y. H., Jones, D. W., Holzhauer, S., Hanson, M. S., Machogu, E. M., Brousseau, D. C., Hogg, N., Densmore, J. C., et al. (2014) · Blood · doi:10.1182/blood-2014-04-560813 · Cited by 59
Chaturvedi, S., Ghafuri, D. L., Glassberg, J., Kassim, A. A., Rodeghier, M., & DeBaun, M. R. (2016) · American Journal of Hematology · doi:10.1002/ajh.24539 · Cited by 60
Allali, S., Rignault‐Bricard, R., de Montalembert, M., Taylor, M., Bouceba, T., Hermine, O., & Maciel, T. T. (2022) · Blood · doi:10.1182/blood.2021014894 · Cited by 64
Chaturvedi, S., Ghafuri, D. L., Jordan, N., Kassim, A. A., Rodeghier, M., & DeBaun, M. R. (2018) · American Journal of Hematology · doi:10.1002/ajh.25202 · Cited by 59
Arumugam, P. I., Mullins, E. S., Shanmukhappa, S. K., Monia, B. P., Loberg, A., Shaw, M. A., Rizvi, T. A., Wansapura, J. P., Degen, J. L., & Malik, P. (2015) · Blood · doi:10.1182/blood-2015-01-625707 · Cited by 63
Vinchi, F., Sparla, R., Passos, S., Sharma, R., Vance, S. Z., Zreid, H., Juaidi, H., Manwani, D. G., Yazdanbakhsh, K., Nandi, V., et al. (2021) · British Journal of Haematology · doi:10.1111/bjh.17361 · Cited by 57
Hemopexin in severe inflammation and infection: mouse models and human diseases
Lin, T., Maita, D., Thundivalappil, S. R., Riley, F. E., Hambsch, J., Marter, L. J. V., Christou, H. A., Berra, L. M., Fagan, S. P., Christiani, D. C., et al. (2015) · Critical Care · doi:10.1186/s13054-015-0885-x · Cited by 56
Kassa, T., Jana, S., Strader, M. B., Meng, F., Jia, Y., Wilson, M. T., & Alayash, A. I. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.651257 · Cited by 57
Wagener, B. M., Hu, P. J., Oh, J., Evans, C. A., Richter, J. R., Honavar, J., Brandon, A. P., Creighton, J. R., Stephens, S. W., Morgan, C. J., et al. (2018) · PLoS Medicine · doi:10.1371/journal.pmed.1002522 · Cited by 56
Merle, N. S., Grünenwald, A., Figueres, L., Chauvet, S., Daugan, M. V., Knockaert, S., Robe-Rybkine, T., Noé, R., May, O., Frimat, M., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00179 · Cited by 55
Heme‐related molecules induce rapid production of neutrophil extracellular traps
Kono, M., Saigo, K., Takagi, Y., Takahashi, T., Kawauchi, S., Wada, A., Hashimoto, M., Minami, Y., Imoto, S., Takenokuchi, M., et al. (2014) · Transfusion · doi:10.1111/trf.12700 · Cited by 54
Hemin Causes Lung Microvascular Endothelial Barrier Dysfunction by Necroptotic Cell Death
Singla, S., Sysol, J. R., Dille, B., Jones, N., Chen, J., & Machado, R. F. (2017) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2016-0287oc · Cited by 55
Blood rheological abnormalities in sickle cell anemia
Connes, P., Renoux, C., Romana, M., Abkarian, M., Joly, P., Martin, C., Hardy‐Dessources, M., & Ballas, S. K. (2018) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-189005 · Cited by 55
Stapley, R. D., Rodriguez, C. A., Oh, J., Honavar, J., Brandon, A. P., Wagener, B. M., Marques, M. B., Weinberg, J. A., Kerby, J. D., Pittet, J., et al. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.04.025 · Cited by 51
HO-1hi patrolling monocytes protect against vaso-occlusion in sickle cell disease
Liu, Y., Jing, F., Yi, W., Mendelson, A., Shi, P., Walsh, R., Friedman, D. F., Minniti, C., Manwani, D., Chou, S. T., et al. (2018) · Blood · doi:10.1182/blood-2017-12-819870 · Cited by 51
Comparative Analysis of Pain Behaviours in Humanized Mouse Models of Sickle Cell Anemia
Lei, J., Benson, B. A., Tran, H., Ofori-Acquah, S. F., & Gupta, K. (2016) · PLoS ONE · doi:10.1371/journal.pone.0160608 · Cited by 52
Self-citationVercellotti, G. M., Zhang, P., Nguyen, J., Abdulla, F. A., Chen, C., Nguyen, P., Nowotny, C., Steer, C. J., Smith, A., & Belcher, J. D. (2016) · Molecular Medicine · doi:10.2119/molmed.2016.00063 · Cited by 51
Lei, J., Paul, J. A., Wang, Y., Gupta, M., Vang, D., Thompson, S. T., Jha, R., Nguyen, J., Valverde, Y., Lamarre, Y., et al. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7913 · Cited by 51
Hounkpe, B. W., Fiusa, M. M. L., Colella, M. P., da Costa, L. N. G., Benatti, R. O., Saad, S. T. O., Costa, F. F., Santos, M. N. N., & Paula, E. V. D. (2015) · Scientific Reports · doi:10.1038/srep17822 · Cited by 49
Krishnamoorthy, S., Pace, B. S., Gupta, D., Sturtevant, S., Li, Y., Makala, L., Brittain, J. E., Moore, N., Vieira, B. F., Thullen, T. D., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.96409 · Cited by 48
Noncanonical Roles of Caspase-4 and Caspase-5 in Heme-Driven IL-1β Release and Cell Death
Bolívar, B. E., Brown-Suedel, A. N., Rohrman, B. A., Charendoff, C. I., Yazdani, V., Belcher, J. D., Vercellotti, G. M., Flanagan, J. M., & Bouchier‐Hayes, L. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2000226 · Cited by 48
Morphine for the Treatment of Pain in Sickle Cell Disease
Gupta, M., Msambichaka, L. A., Ballas, S. K., & Gupta, K. (2015) · The Scientific World JOURNAL · doi:10.1155/2015/540154 · Cited by 46
Wang, X., Mendelsohn, L. G., Rogers, H. M., Leitman, S. F., Raghavachari, N., Yang, Y., Yau, Y. Y., Tallack, M. R., Perkins, A. C., Taylor, J. G., et al. (2014) · Blood · doi:10.1182/blood-2013-11-539718 · Cited by 45
Inflammatory targets of therapy in sickle cell disease
Owusu-Ansah, A. T., Ihunnah, C. A., Walker, A. L., & Ofori-Acquah, S. F. (2015) · Translational research · doi:10.1016/j.trsl.2015.07.001 · Cited by 46
Self-citationAltered heme-mediated modulation of dendritic cell function in sickle cell alloimmunization
Godefroy, E., Liu, Y., Shi, P. A., Mitchell, W. B., Cohen, D., Chou, S. T., Manwani, D. G., & Yazdanbakhsh, K. (2016) · Haematologica · doi:10.3324/haematol.2016.147181 · Cited by 44
Hemopexin counteracts systolic dysfunction induced by heme-driven oxidative stress
Ingoglia, G., Sag, C. M., Rex, N., Franceschi, L. D., Vinchi, F., Cimino, J., Petrillo, S., Wagner, S., Kreitmeier, K., Silengo, L., et al. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.04.003 · Cited by 43
Role of TLR4 signaling in the nephrotoxicity of heme and heme proteins
Nath, K. A., Belcher, J. D., Nath, M. C., Grande, J. P., Croatt, A. J., Ackerman, A. W., Katušić, Z. S., & Vercellotti, G. M. (2017) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00432.2017 · Cited by 44
Hypercoagulable state in sickle cell disease
Faës, C., Sparkenbaugh, E., & Pawliński, R. (2018) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-189013 · Cited by 45
Hemopexin deficiency promotes acute kidney injury in sickle cell disease
Ofori-Acquah, S. F., Hazra, R., Orikogbo, O., Crosby, D. E., Flage, B., Ackah, E. B., Lenhart, D., Tan, R. J., Vitturi, D. A., Paintsil, V., et al. (2020) · Blood · doi:10.1182/blood.2019002653 · Cited by 44
Self-citationSickle cell disease: progress towards combination drug therapy
Pace, B. S., Starlard‐Davenport, A., & Kutlar, A. (2021) · British Journal of Haematology · doi:10.1111/bjh.17312 · Cited by 46
Yin, T., He, S., Liu, X., Jiang, W., Ye, T., Lin, Z., Sang, Y., Su, C., Wan, Y., Shen, G., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400643 · Cited by 42
Cell-penetrating peptides selectively targeting SMAD3 inhibit profibrotic TGF-β signaling
Kang, J. H., Jung, M.-Y., Yin, X., Andrianifahanana, M., Hernandez, D. M., & Leof, E. B. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88696 · Cited by 42
Identification of a Heme Activation Site on the MD-2/TLR4 Complex
Belcher, J. D., Zhang, P., Nguyen, J., Kiser, Z. M., Nath, K. A., Hu, J., Trent, J. O., & Vercellotti, G. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01370 · Cited by 41
Vercellotti, G. M., Khan, F. B., Nguyen, J., Chen, C., Bruzzone, C. M., Bechtel, H., Brown, G., Nath, K. A., Steer, C. J., Hebbel, R. P., et al. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00079 · Cited by 38
Platelet activation and ferroptosis mediated NETosis drives heme induced pulmonary thrombosis
NaveenKumar, S. K., Hemshekhar, M., SharathBabu, B. N., Kemparaju, K., Mugesh, G., & Girish, K. S. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166688 · Cited by 37
Bennewitz, M. F., Watkins, S. C., & Sundd, P. (2014) · IntraVital · doi:10.4161/intv.29748 · Cited by 37
Sarode, R., Ballas, S. K., Garcia, A., Kim, H. C., King, K. E., Sachais, B. S., & Williams, L. A. (2016) · Journal of Clinical Apheresis · doi:10.1002/jca.21511 · Cited by 37
Potoka, K. P., Wood, K. C., Baust, J., Bueno, M., Hahn, S. A., Vanderpool, R. R., Bachman, T. N., Mallampalli, G. M., Osei-Hwedieh, D. O., Schrott, V. M., et al. (2017) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2017-0292oc · Cited by 35
Vascularized Microfluidics and the Blood–Endothelium Interface
Hesh, C. A., Qiu, Y., & Lam, W. A. (2019) · Micromachines · doi:10.3390/mi11010018 · Cited by 41
Metadata
- Authors
- Ghosh, S., Adisa, O. A., Chappa, P., Tan, F., Jackson, K. A., Archer, D. R., & Ofori-Acquah, S. F.
- Affiliations
- Emory University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2013-10-01
- Volume
- 123
- Issue
- 11
- Pages
- 4809-4820
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3809772
- OpenAlex
- W2100360129
- Cited by
- 282
- References
- 72
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 14 · 2023: 23 · 2022: 17 · 2021: 29 · 2020: 24 · 2019: 19 · 2018: 25 · 2017: 19 · 2016: 37 · 2015: 23 · 2014: 18 · 2013: 2
- FWCI
- 13.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Emory University
- National Heart, Lung, and Blood Institute (R01HL106192, K02HL088026, U01HL117721)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- acute chest syndrome, sickle cell disease, hemolysis, TLR4, hemopexin, acute lung injury, respiratory failure, TLR4 inhibition, lung injury pathogenesis, bone marrow chimeras
- MeSH terms
- Anemia, Sickle Cell, Animals, Disease Models, Animal, Extracellular Space, Hemin, Hemoglobin, Sickle, Hemolysis, Hemopexin, Humans, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, Recombinant Proteins, Sickle Cell Trait, Sulfonamides, Mice, Knockout, Toll-Like Receptor 4, Mice, Acute Chest Syndrome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
