Cited by 282Hemoglobinopathies and Related DisordersHemoglobin structure and functionBlood groups and transfusion

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Extracellular hemin crisis triggers acute chest syndrome in sickle mice

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Ghosh, Samit, Adisa, Olufolake Adetoro, Chappa, Prasanthi, Tan, Fang, Jackson, Kesmic Ann, Archer, David Robert, Ofori-Acquah, Solomon Fiifi·2013·Journal of Clinical Investigation

DOI 10.1172/jci64578PMC PMC3809772

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Abstract

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.

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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
Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis: The ACCESS Randomized Trial
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
The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease
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
The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease
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
The Roles of Two IκB Kinase-related Kinases in Lipopolysaccharide and Double Stranded RNA Signaling and Viral Infection
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
Acute Chest Syndrome in Sickle Cell Disease: Clinical Presentation and Course
Vichinsky, E. P., Styles, L. A., Colangelo, L. H., Wright, E. C., Castro, O., Nickerson, B., & Disease, T. C. S. O. S. C. (1997) · Blood · doi:10.1182/blood.v89.5.1787 · Cited by 573 · cited 3×
“In the Cooperative Study of Sickle Cell Disease, severe acute hemolysis was the only predictor of sudden death due to ACS (15).”
Influential
Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria
Pamplona, A., Ferreira, A., Balla, J., Jeney, V., Balla, G., Epiphanio, S., Chora, Â., Rodrigues, C. D., Gregoire, I. P., Cunha-Rodrigues, M., et al. (2007) · Nature Medicine · doi:10.1038/nm1586 · Cited by 560
A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis*
Rice, T. W., Wheeler, A. P., Bernard, G. R., Vincent, J.-L., Angus, D. C., Aikawa, N., Demeyer, I., Sainati, S., Amlot, N., Cao, C., et al. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181e7c5c9 · Cited by 512
A Central Role for Free Heme in the Pathogenesis of Severe Sepsis
Larsen, R., Gozzelino, R., Jeney, V., Tokaji, L., Bozza, F. A., Japiassú, A. M., Bonaparte, D., Cavalcante, M. M., Chora, Â., Ferreira, A., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001118 · Cited by 483
Pulmonary Complications of Sickle Cell Disease
Gladwin, M. T., & Vichinsky, E. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0804411 · Cited by 470
Transgenic Knockout Mice with Exclusively Human Sickle Hemoglobin and Sickle Cell Disease
Pászty, C., Brion, C. M., Manci, E., Witkowska, H. E., Stevens, M. E., Mohandas, N., & Rubin, E. M. (1997) · Science · doi:10.1126/science.278.5339.876 · Cited by 467
Mortality in Sickle Cell Disease
Rodgers, G. P., Walker, E. C., & Podgor, M. J. (1994) · New England Journal of Medicine · doi:10.1056/nejm199410133311515 · Cited by 459
Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator-induced lung injury
Belperio, J. A., Keane, M. P., Burdick, M. D., Londhe, V. A., Xue, Y., Li, K., Phillips, R. J., & Strieter, R. M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15849 · Cited by 450
Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase
Wagener, F. A. D. T. G., Eggert, A. O., Boerman, O. C., Oyen, W. J. G., Verhofstad, A. A. J., Abraham, N. G., Adema, G. J., van Kooyk, Y., de Witte, T., & Figdor, C. G. (2001) · Blood · doi:10.1182/blood.v98.6.1802 · Cited by 423
Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice
Kaul, D. K., & Hebbel, R. P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9225 · Cited by 416
Exchange of Heme among Hemoglobins and between Hemoglobin and Albumin
Bunn, H. F., & Jandl, J. H. (1968) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)93628-8 · Cited by 415
Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury
Looney, M. R., Nguyen, J. X., Hu, Y., Ziffle, J. V., Lowell, C. A., & Matthay, M. A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38432 · Cited by 397
Methemoglobin—It's not just blue: A concise review
Umbreit, J. N. (2006) · American Journal of Hematology · doi:10.1002/ajh.20738 · Cited by 380
Brief Report: Plasma Concentrations of Hemopexin, Haptoglobin and Heme in Patients with Various Hemolytic Diseases
Müller‐Eberhard, U., Javid, J., Liem, H. H., von Hanstein, A. S., & Hanna, M. (1968) · Blood · doi:10.1182/blood.v32.5.811.811 · Cited by 329
Correction of sickle cell disease by homologous recombination in embryonic stem cells
Wu, L.-C., Sun, C., Ryan, T. M., Pawlik, K. M., Ren, J., & Townes, T. M. (2006) · Blood · doi:10.1182/blood-2006-02-004812 · Cited by 327
Neutrophils and their Fc receptors are essential in a mouse model of transfusion-related acute lung injury
Looney, M. R. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27238 · Cited by 310
Accelerated autoxidation and heme loss due to instability of sickle hemoglobin.
Hebbel, R. P., Morgan, W. T., Eaton, J. W., & Hedlund, B. E. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.1.237 · Cited by 306
Heme oxygenase-1 affords protection against noncerebral forms of severe malaria
Seixas, E., Gozzelino, R., Chora, Â., Ferreira, A., Silva, G., Larsen, R., Rebelo, S., Penido, C., Smith, N. R., Coutinho, A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903419106 · Cited by 275
Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice
Belcher, J. D. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26857 · Cited by 267
COMMD Proteins, a Novel Family of Structural and Functional Homologs of MURR1
Burstein, E., Hoberg, J. E., Wilkinson, A. S., Rumble, J. M., Csomos, R. A., Komarck, C. M., Maine, G. N., Wilkinson, J. C., Mayo, M. W., & Duckett, C. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501928200 · Cited by 258
Analysis of binding site for the novel small‐molecule TLR4 signal transduction inhibitor TAK‐242 and its therapeutic effect on mouse sepsis model
Takashima, K., Matsunaga, N., Yoshimatsu, M., Hazeki, K., Kaisho, T., Uekata, M., Hazeki, O., Akira, S., Iizawa, Y., & Ii, M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00297.x · Cited by 247
Beneficial Effect of Intravenous Dexamethasone in Children With Mild to Moderately Severe Acute Chest Syndrome Complicating Sickle Cell Disease
Bernini, J. C., Rogers, Z. R., Sandler, E. S., REISCH, J. S., Quinn, C. T., & Buchanan, G. R. (1998) · Blood · doi:10.1182/blood.v92.9.3082 · Cited by 228
Prevention by polymyxin B of endotoxin lethality in mice
Rifkind, D. (1967) · Journal of Bacteriology · doi:10.1128/jb.93.4.1463-1464.1967 · Cited by 185
Oxidative Stress and Induction of Heme Oxygenase-1 in the Kidney in Sickle Cell Disease
Nath, K. A., Grande, J. P., Haggard, J. J., Croatt, A. J., Katušić, Z. S., Solovey, A. N., & Hebbel, R. P. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64037-0 · Cited by 185
ACUTE CHEST SYNDROME IN SICKLE-CELL DISEASE
Davies, S. C., Win, A. A., Luce, P. J., Riordan, J. F., & Brozović, M. (1984) · The Lancet · doi:10.1016/s0140-6736(84)90193-4 · Cited by 181
Therapeutic effects of TAK-242, a novel selective Toll-like receptor 4 signal transduction inhibitor, in mouse endotoxin shock model
Sha, T., Sunamoto, M., Kitazaki, T., Sato, J., Ii, M., & Iizawa, Y. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.06.027 · Cited by 177
Reconstructing sickle cell disease: A data‐based analysis of the “hyperhemolysis paradigm” for pulmonary hypertension from the perspective of evidence‐based medicine
Hebbel, R. P. (2010) · American Journal of Hematology · doi:10.1002/ajh.21952 · Cited by 171
Mechanism of hemolysis induced by ferriprotoporphyrin IX
Chou, A. C., & Fitch, C. D. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110302 · Cited by 168
NKT cells mediate pulmonary inflammation and dysfunction in murine sickle cell disease through production of IFN-γ and CXCR3 chemokines
Wallace, K. L., Marshall, M. A., Ramos, S. I., Lannigan, J. A., Field, J. J., Strieter, R. M., & Linden, J. M. (2009) · Blood · doi:10.1182/blood-2009-02-205492 · Cited by 153
Adenosine A2A receptors induced on iNKT and NK cells reduce pulmonary inflammation and injury in mice with sickle cell disease
Wallace, K. L., & Linden, J. M. (2010) · Blood · doi:10.1182/blood-2010-06-290643 · Cited by 152
Acute Chest Syndrome in Adults With Sickle Cell Disease
Maître, B., Habibi, A., Roudot‐Thoraval, F., Bachir, D., Belghiti, D., Galactéros, F., & Godeau, B. (2000) · CHEST Journal · doi:10.1378/chest.117.5.1386 · Cited by 130
Hemopexin Prevents Endothelial Damage and Liver Congestion in a Mouse Model of Heme Overload
Vinchi, F., Gastaldi, S., Silengo, L., Altruda, F., & Tolosano, E. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.071130 · Cited by 125
Hemolysis of mouse erythrocytes by ferriprotoporphyrin IX and chloroquine. Chemotherapeutic implications.
Chou, A. C., & Fitch, C. D. (1980) · Journal of Clinical Investigation · doi:10.1172/jci109925 · Cited by 122
Acute chest syndrome in children with sickle cell disease. A retrospective analysis of 100 hospitalized cases.
Sprinkle, R. H., Cole, T., Smith, S., & Buchanan, G. R. (1986) · PubMed · Cited by 109
The Acute Chest Syndrome in Sickle Cell Disease: Possible Role of Nitric Oxide in Its Pathophysiology and Treatment
Gladwin, M. T., Schechter, A. N., Shelhamer, J. H., & Ognibene, F. P. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.159.5.9810094 · Cited by 96
Association between plasma free haem and incidence of vaso‐occlusive episodes and acute chest syndrome in children with sickle cell disease
Adisa, O. A., Hu, Y., Ghosh, S., Aryee, D., Osunkwo, I., & Ofori‐Acquah, S. F. (2013) · British Journal of Haematology · doi:10.1111/bjh.12445 · Cited by 88
Self-citation
Heme oxygenase-1 gene promoter polymorphism is associated with reduced incidence of acute chest syndrome among children with sickle cell disease
Bean, C. J., Boulet, S. L., Ellingsen, D., Pyle, M., Barron‐Casella, E. A., Casella, J. F., Payne, A. B., Driggers, J., Trau, H. A., Yang, G., et al. (2012) · Blood · doi:10.1182/blood-2011-06-361642 · Cited by 83
Self-citation
Hypoxia-induced acute lung injury in murine models of sickle cell disease
Pritchard, K. A., Ou, J., Ou, Z., Shi, Y., Franciosi, J. P., Signorino, P. R., Kaul, S., Ackland-Berglund, C. E., Witte, K., Holzhauer, S., et al. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00288.2002 · Cited by 79
Inhaled nitric oxide protects transgenic SAD mice from sickle cell disease-specific lung injury induced by hypoxia/reoxygenation
Franceschi, L. D. (2003) · Blood · doi:10.1182/blood-2002-07-2135 · Cited by 79
Comparative Oxidation of Hemoglobins A and S
Sheng, K., Shariff, M., & Hebbel, R. P. (1998) · Blood · doi:10.1182/blood.v91.9.3467 · Cited by 75
Detection of hemin release during hemoglobin S denaturation
Liu, S., Zhai, S., & Palek, J. (1988) · Blood · doi:10.1182/blood.v71.6.1755.1755 · Cited by 73
Pulse-oximetry accurately predicts lung pathology and the immune response during influenza infection
Verhoeven, D. E., Teijaro, J. R., & Färber, D. L. (2009) · Virology · doi:10.1016/j.virol.2009.05.004 · Cited by 66
Enhanced Pulmonary and Systemic Response to Endotoxin in Transgenic Sickle Mice
Holtzclaw, J. D., Jack, D. L., Aguayo, S. M., Eckman, J. R., Roman, J., & Hsu, L. L.-Y. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200302-224oc · Cited by 62
Differential effects of chloral hydrate- and ketamine/xylazine-induced anesthesia by the s.c. route
Rodrigues, S. F., Oliveira, M. A., Martins, J. O., Sannomiya, P., Tostes, R. C., Nigro, D., de Carvalho, M. H. C., & Fortes, Z. B. (2006) · Life Sciences · doi:10.1016/j.lfs.2006.05.019 · Cited by 60
Spatiotemporal Dysfunction of the Vascular Permeability Barrier in Transgenic Mice with Sickle Cell Disease
Ghosh, S., Tan, F., & Ofori-Acquah, S. F. (2012) · Anemia · doi:10.1155/2012/582018 · Cited by 55
Self-citation
Blood gases and energy metabolites in mouse blood before and after cerebral ischemia: the effects of anesthetics
Schwarzkopf, T. M., Horn, T., Lang, D., & Klein, J. (2013) · Experimental Biology and Medicine · doi:10.1258/ebm.2012.012261 · Cited by 51
Increased F2 Isoprostanes in the Acute Chest Syndrome of Sickle Cell Disease as a Marker of Oxidative Stress
Klings, E. S., Christman, B. W., McClung, J. P., Stucchi, A. F., McMahon, L. C., BRAUER, M., & Farber, H. W. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.164.7.2101020 · Cited by 46
Utilization of pulse oximetry for the study of the inhibitory effects of antiviral agents on influenza virus in mice
Sidwell, R. W., Huffman, J. H., Gilbert, J., Moscon, B. J., Pedersen, G., Burger, R., & Warren, R. P. (1992) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.36.2.473 · Cited by 46
Inhaled Nitric Oxide Improves Survival Rates during Hypoxia in a Sickle Cell (SAD) Mouse Model
Martinez-Ruiz, R., Montero-Huerta, P., Hromi, J., & Head, C. A. (2001) · Anesthesiology · doi:10.1097/00000542-200106000-00028 · Cited by 46
Hemopexin Metabolism in Sickle-Cell Disease, Porphyrias and Control Subjects — Effects of Heme Injection
Wochner, R. D., Spilberg, I., Iio, A., Liem, H. H., & Müller‐Eberhard, U. (1974) · New England Journal of Medicine · doi:10.1056/nejm197404112901503 · Cited by 43
Hospital volume, hospital teaching status, patient socioeconomic status, and outcomes in patients hospitalized with sickle cell disease
McCavit, T. L., Lin, H., Zhang, S., Ahn, C. W., Quinn, C. T., & Flores, G. (2011) · American Journal of Hematology · doi:10.1002/ajh.21977 · Cited by 42
Gene-centric association study of acute chest syndrome and painful crisis in sickle cell disease patients
Galarneau, G., Coady, S., Garrett, M. E., Jeffries, N. O., Puggal, M. A., Paltoo, D. N., Soldano, K. L., Guasch, A., Ashley‐Koch, A. E., Telen, M. J., et al. (2013) · Blood · doi:10.1182/blood-2013-01-478776 · Cited by 41
Sepsis study failure highlights need for trial design rethink
Tse, M. T. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4016 · Cited by 41
Impaired erythrocyte methemoglobin reduction in sickle cell disease: dependence of methemoglobin reduction on reduced nicotinamide adenine dinucleotide content
Zerez, C., Lachant, N., & Tanaka, K. (1990) · Blood · doi:10.1182/blood.v76.5.1008.1008 · Cited by 34
Acute Chest Syndrome in Adult Afro-Caribbean Patients With Sickle Cell Disease
van Agtmael, M. A. (1994) · Archives of Internal Medicine · doi:10.1001/archinte.1994.00420050119011 · Cited by 32
Global Gene Expression Profiling of Endothelium Exposed to Heme Reveals an Organ-Specific Induction of Cytoprotective Enzymes in Sickle Cell Disease
Ghosh, S., Tan, F., Yu, T., Li, Y., Adisa, O. A., Mosunjac, M. I., & Ofori-Acquah, S. F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018399 · Cited by 31
Self-citation
Acute chest syndrome in adult Afro-Caribbean patients with sickle cell disease. Analysis of 81 episodes among 53 patients
van Agtmael, M. A. (1994) · Archives of Internal Medicine · doi:10.1001/archinte.154.5.557 · Cited by 31
ShRNA-Targeted COMMD7 Suppresses Hepatocellular Carcinoma Growth
Zheng, L., Liang, P., Li, J., Huang, X., Liu, S., Zhao, H., Han, K., & Wang, Z. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045412 · Cited by 27
Methaemalbumin formation in sickle cell disease: effect on oxidative protein modification and HO‐1 induction
Hanson, M. S., Piknova, B., Keszler, Á., Diers, A. R., Wang, X., Gladwin, M. T., Hillery, C. A., & Hogg, N. (2011) · British Journal of Haematology · doi:10.1111/j.1365-2141.2011.08738.x · Cited by 25
The acute chest syndrome of sickle cell disease
Desai, P. C., & Ataga, K. I. (2013) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2013.783570 · Cited by 23
Antisickling fetal hemoglobin reduces hypoxia-inducible factor-1α expression in normoxic sickle mice: microvascular implications
Kaul, D. K., Fabry, M. E., Suzuka, S. M., & Zhang, X. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00296.2012 · Cited by 22
Effect of Synchronized Intermittent Mandatory Ventilation on Respiratory Workload in Infants after Cardiac Surgery
Imanaka, H., Nishimura, M., Miyano, H., Uemura, H., & Yagihara, T. (2001) · Anesthesiology · doi:10.1097/00000542-200110000-00016 · Cited by 10
NOTICE TO CORRESPONDENTS.
NA (1823) · The Lancet · doi:10.1016/s0140-6736(01)18847-1 · Cited by 2

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Authors: Ghosh, S., Adisa, O. A., Chappa, P., Tan, F., Jackson, K. A., Archer, D. R., & Ofori-Acquah, S. F.
Affiliations: Emory University (US)
ORCID: Ghosh, Samit
Tan, Fang
Archer, David Robert
Ofori-Acquah, Solomon Fiifi
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2013-10-01
Volume: 123
Issue: 11
Pages: 4809-4820
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci64578
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

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Extracellular hemin crisis triggers acute chest syndrome in sickle mice

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