Effect of Quercetin on Lipopolysaccharide and Hydroxyurea Induced Lactate Dehydrogenase Release from Immortalize Mouse Aortic Endothelial Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4846-4846
Author(s):  
Zachary Monroe Kiser ◽  
Jacqueline Monroe Hibbert ◽  
Alexander Quarshie
Keyword(s):  
Endothelial Cells ◽  
Lactate Dehydrogenase ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Damage ◽  
Vascular Endothelial ◽  
Cell Disease ◽  
Aortic Endothelial Cells ◽  
Dietary Flavonoid

Abstract Background: A higher than normal basal inflammatory state is characteristic of sickle cell disease (SCD). Hydroxyurea (HU) is the only FDA approved drug for SCD. However, HU is a chemotherapy drug and is therefore naturally cytotoxic, often inducing apoptosis. Chronic inflammation in sickle cell patients is invariably associated with injury to the vascular endothelium. Quercetin is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Hypothesis: The dietary flavonoid quercetin will decrease cytotoxic effects of Lipopolysaccharide and HU induced cell damage to vascular endothelial cells. Aims: 1. to develop an in vitro inflammatory model simulating chronic baseline inflammation observed in sickle cell disease. 2. to test the effect of the physiological dose of hydroxyurea (HU), on the inflammatory model. 3. to examine the role of quercetin (QCT), a dietary flavonoid with anti-oxidative and anti-inflammatory characteristics, for reducing the inflammation. Methods: Lipopolysaccharide (LPS) was used to induce inflammation in immortalized mouse aortic endothelial cells (iMAECs), providing an in vitro model of inflamed endothelial cells. The cells were exposed to LPS throughout the entire experiment. Interventions included treating the LPS exposed cells with QCT, HU, or QCT + HU over 50 hours. The 50-hour period included 24 hours of varying treatments, followed by two hours of hypoxic exposure and then 24 hours under normal aerobic exposure. Untreated cells (controls) provided a comparison. Data analyses included comparisons of control cells with the inflammatory model, and pairwise comparisons between the inflammatory model and the different treatments. In this experiment lactate dehydrogenase (LDH) was measured by colorimetric assay, as an indication of cell damage. Results: At the end of the experiment, the LDH level for the inflammatory model was significantly higher than LDH for the control cells (P = 0.0005) fig 1. Treatment with 30 micromoles QCT gleaned a trend toward reduced LDH compared with the inflammatory model (p = 0.1) fig 2. LDH was significantly higher after treatment with 100 micromoles HU compared with the inflammatory model (p = 0.0005) Fig 3. However, LDH was significantly reduced after treatment with a combination of 30 micromoles QCT/100 micromoles HU, compared with 100 micromoles HU alone (p = 0.0008) fig 3. Conclusions: These results suggest that quercetin may be effective against vascular endothelial cell damage for iMAECs in vitro. It also shows promise in preventing HU-induced cytotoxicity, which was a surprising finding from these results. This latter finding is interesting, and should be given more consideration, since HU is the only FDA-approved drug for treating sickle cell patients, and its use is rapidly increasing. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

scholarly journals Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3376 ◽  
Author(s):  
Zachary M. Kiser ◽  
Monica D.M. McGee ◽  
Racquel J. Wright ◽  
Alexander Quarshie ◽  
Gale W. Newman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Sickle Cell ◽  
Cell Damage ◽  
Vascular Endothelial Cell ◽  
Hypoxic Exposure ◽  
Vascular Endothelial ◽  
Aortic Endothelial Cells ◽  
Dietary Flavonoid ◽  
Aortic Endothelial

BackgroundChronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT) is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Our hypothesis is that dietary QCT will decrease cytotoxic effects of lipopolysaccharide (LPS) and HU induced vascular cell damage.MethodsLipopolysaccharide (LPS) was used to induce inflammation in immortalized mouse aortic endothelial cells (iMAECs), providing an in vitro model of inflamed endothelial cells. The cells were exposed to LPS throughout the entire experiment. Interventions included treating the LPS exposed cells with QCT, HU, or QCT + HU over 50 hours. The 50-hour period included 24 hours of varying treatments, followed by two hours of hypoxic exposure and then 24 hours under normal aerobic exposure.ResultsLDH level was significantly higher for LPS treated versus untreated cells (P = 0.0004). LPS plus 30 micromole QCT reduced the LDH (p = 0.1, trend), whereas LPS plus 100 micromoles HU, significantly increased LDH (p = 0.0004). However, LPS plus treatment with 30 micromoles QCT/100 micromoles HU, significantly reduced LDH, compared with HU alone (p = 0.0002).DiscussionThese results suggest that quercetin may be effective against vascular endothelial cell damage for iMAECsin vitro. In particular, it shows promise in preventing HU-induced cytotoxicity, surprisingly found from these results. This latter finding is important, and should be given more consideration, since HU is the only FDA-approved drug for treating sickle cell patients, and its use is rapidly increasing.

scholarly journals Inhibition of cell adhesion by anti–P-selectin aptamer: a new potential therapeutic agent for sickle cell disease

Blood ◽  
2011 ◽  
Vol 117 (2) ◽  
pp. 727-735 ◽  
Author(s):  
Diana R. Gutsaeva ◽  
James B. Parkerson ◽  
Shobha D. Yerigenahally ◽  
Jeffrey C. Kurz ◽  
Robert G. Schaub ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Therapeutic Agent ◽  
Critical Role ◽  
High Specificity ◽  
Cell Disease ◽  
Adhesive Interactions

Abstract Adhesive interactions between circulating sickle red blood cells (RBCs), leukocytes, and endothelial cells are major pathophysiologic events in sickle cell disease (SCD). To develop new therapeutics that efficiently inhibit adhesive interactions, we generated an anti–P-selectin aptamer and examined its effects on cell adhesion using knockout-transgenic SCD model mice. Aptamers, single-stranded oligonucleotides that bind molecular targets with high affinity and specificity, are emerging as new therapeutics for cardiovascular and hematologic disorders. In vitro studies found that the anti–P-selectin aptamer exhibits high specificity to mouse P-selectin but not other selectins. SCD mice were injected with the anti–P-selectin aptamer, and cell adhesion was observed under hypoxia. The anti–P-selectin aptamer inhibited the adhesion of sickle RBCs and leukocytes to endothelial cells by 90% and 80%, respectively. The anti–P-selectin aptamer also increased microvascular flow velocities and reduced the leukocyte rolling flux. SCD mice treated with the anti–P-selectin aptamer demonstrated a reduced mortality rate associated with the experimental procedures compared with control mice. These results demonstrate that anti–P-selectin aptamer efficiently inhibits the adhesion of both sickle RBCs and leukocytes to endothelial cells in SCD model mice, suggesting a critical role for P-selectin in cell adhesion. Anti–P-selectin aptamer may be useful as a novel therapeutic agent for SCD.

The Adhesion of Sickle Cell Disease Neutrophils to Endothelial Layers, In Vitro, Is Mediated by the Mac-1, LFA-1 and VLA-4 Integrins.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2264-2264 ◽  
Author(s):  
Andreia A. Canalli ◽  
Renata F. Proenca ◽  
Sara T.O. Saad ◽  
Nicola Conran ◽  
Fernando F. Costa
Keyword(s):  
Endothelial Cells ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Umbilical Vein ◽  
In Vivo Studies ◽  
Integrin Subunit ◽  
Cell Disease ◽  
Inflammatory Conditions ◽  
Tnf Α

Abstract Leukocytes may have a propagating and, possibly, initiating role in sickle cell disease (SCD) vaso-occlusion. In vivo studies suggest that adherent leukocytes capture sickle erythrocytes in the microcirculation and in vitro studies demonstrate an increased ability of SCD neutrophils (neu) to adhere to fibronectin, endothelial cells and endothelial proteins. Previous studies suggest that the expressions of the major neu integrins, CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1) may only be upregulated on the surface of SCD neu following their stimulation, indicating that alterations in integrin function (affinity or avidity) contribute to alter SCD neu adhesion. The objective of this study was to identify the integrins responsible for altered SCD neu adhesion. Neus were isolated from the peripheral blood of healthy controls and SCD individuals in steady state over ficoll-paque gradients. Cell adhesion (2×106cells/ml in RPMI) to cultured human umbilical vein endothelial cells (HUVEC) at confluence was assessed using static adhesion assays (30min, 37°C, 5%CO2). Neus from SCD patients demonstrated a significantly greater adhesion to HUVEC than control neus (20.2±2.8% compared to 11.2±1.0%; n≥7; p<0.03; Mann Whitney test). Subsequently, cells were co-incubated with adhesion molecule-blocking monoclonal antibodies (mAbs) during assays. Control neu adhesion to HUVEC was significantly inhibited by the anti-CD11b mAb (6.7±1.5%;n=6; P<0.05, paired t test), but not by mAbs against CD11a, the VLA-4-integrin subunit, CD49d, or a non-specific negative control mAb (neg control) (data not shown). In contrast, the adhesion of SCD neus to HUVEC was significantly inhibited by both the anti-CD11a and the anti-CD11b mAbs (20.2±2.8% reduced to 11.4±1.2% and 9.1±1.5%; n=9; P<0.01 and P<0.001, respect.). Interestingly, a mAb against CD49d was also found to significantly decrease SCD neu adhesion to HUVEC (10.4±1.1%; n=9; P<0.01), while the neg control mAb did not significantly affect SCD neu adhesion (data not shown). Following the stimulation of HUVEC with TNF-α (10 ng/ml) (3h, 37°C, 5%CO2) to simulate an endothelial layer under inflammatory conditions, the adhesions of control and SCD neus were increased but statistically similar (38.4±2.9% and 34.4±5.0%; n≥4, respect.). Under these conditions anti-CD11a and CD11b mAbs significantly inhibited control neu adhesion to HUVEC (reduced to 28.8±2.9% and 19.6±4.6%; n=4; P<0.01 and P<0.05, respect.). In contrast, SCD neu adhesion to HUVEC was significantly inhibited by mAbs for CD11a (19.5±2.6%; n=6; p<0.01) and CD11b (15.2±2.0%; n=6; p<0.001). The anti-CD49d, but not the neg control mAb, also significantly decreased SCD neu adhesion to TNF-α-stimulated HUVEC (19.5±3.7%; n=6; p<0.05). In conclusion, data indicate that control neu adhesion to endothelial cells appears mainly to be mediated by the Mac-1 (CD11b/18) integrin with a contribution from the LFA-1 integrin (CD11a/18) under inflammatory conditions. In contrast, SCD neu adhesion to endothelium (under both basal and stimulated conditions), at least in vitro, appears to be mediated by the Mac-1 and LFA-1 integrins and, interestingly, by VLA-4 (CD49d/CD29), an integrin found expressed at low levels on neus during certain inflammatory conditions. We speculate that alterations in the affinity/ avidity of these molecules contribute to SCD neu adhesion. Approaches to inhibit the adhesion of all three integrins may be important for preventing leukocyte adhesion to the vascular endothelium and, in turn, vaso-occlusion.

Hypoxia-induced acute lung injury in murine models of sickle cell disease

2004 ◽  
Vol 286 (4) ◽  
pp. L705-L714 ◽  
Author(s):  
Kirkwood A. Pritchard ◽  
Jingsong Ou ◽  
Zhijun Ou ◽  
Yang Shi ◽  
James P. Franciosi ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Lung Injury ◽  
Sickle Cell ◽  
Globin Gene ◽  
Heat Shock Protein 90 ◽  
Cell Disease ◽  
Vascular Congestion ◽  
Nitrite Nitrate ◽  
Endothelial Nitric Oxide

Vaso-occlusive events are the major source of morbidity and mortality in sickle cell disease (SCD); however, the pathogenic mechanisms driving these events remain unclear. Using hypoxia to induce pulmonary injury, we investigated mechanisms by which sickle hemoglobin increases susceptibility to lung injury in a murine model of SCD, where mice either exclusively express the human α/sickle β-globin (hαβS) transgene (SCD mice) or are heterozygous for the normal murine β-globin gene and express the hαβStransgene (mβ+/-, hαβS+/-; heterozygote SCD mice). Under normoxia, lungs from the SCD mice contained higher levels of xanthine oxidase (XO), nitrotyrosine, and cGMP than controls (C57BL/6 mice). Hypoxia increased XO and nitrotyrosine and decreased cGMP content in the lungs of all mice. After hypoxia, vascular congestion was increased in lungs with a greater content of XO and nitrotyrosine. Under normoxia, the association of heat shock protein 90 (HSP90) with endothelial nitric oxide synthase (eNOS) in lungs of SCD and heterozygote SCD mice was decreased compared with the levels of association in lungs of controls. Hypoxia further decreased association of HSP90 with eNOS in lungs of SCD and heterozygote SCD mice, but not in the control lungs. Pretreatment of rat pulmonary microvascular endothelial cells in vitro with xanthine/XO decreased A-23187-stimulated nitrite + nitrate production and HSP90 interactions with eNOS. These data support the hypotheses that hypoxia increases XO release from ischemic tissues and that the local increase in XO-induced oxidative stress can then inhibit HSP90 interactions with eNOS, decreasing ·NO generation and predisposing the lung to vaso-occlusion.

Impact of sickle cell anaemia on cardiac chamber size in the paediatric population

2016 ◽  
Vol 27 (5) ◽  
pp. 918-924 ◽  
Author(s):  
Philippe M. Adjagba ◽  
Gaston Habib ◽  
Nancy Robitaille ◽  
Yves Pastore ◽  
Marie-Josée Raboisson ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Sickle Cell Disease ◽  
Left Ventricle ◽  
Right Ventricle ◽  
Sickle Cell ◽  
Myocardial Performance ◽  
Cell Disease ◽  
Left Ventricle Mass ◽  
Cardiac Chamber ◽  
Chamber Size

AbstractPurposeSickle cell disease is known to cause various degrees of vasculopathy, including impact on heart function. The aims of this single-centre, retrospective study were to assess cardiac chamber size and function and the relationship with haematological indices such as haemoglobin, aspartate aminotransferase, reticulocytosis and bilirubin, lactate dehydrogenase in sickle cell disease.MethodsRight ventricle and left ventricle diastolic diameters, left ventricle mass estimate, left ventricle shortening fraction, myocardial performance index, and an index of myocardial relaxation (E/E’) were calculated and correlated with haematological parameters.ResultsA total of 110 patients (65% haemoglobin SS, 29% haemoglobin SC) were studied at a mean age of 12.14±5.26 years. Right ventricle dilatation and left ventricle dilatation were present in 61.5 and 42.9%, respectively. Left ventricle mass was abnormal in 21.9%; all patients had normal myocardial performance index, 31.4% had abnormal E/E’, and left ventricle shortening fraction was low in 38.1%. Cardiac dilatation was best correlated with haemoglobin, aspartate aminotransferase, reticulocytosis and bilirubin. Best subset regression analysis yielded significant additional prediction for right ventricle or left ventricle dilatation with haemoglobin, bilirubin, and lactate dehydrogenase. Abnormal E/E’ was solely predictable with haemoglobin level. Hydroxyurea-treated patients had improved diastolic function.ConclusionRight ventricle dilatation was more prevalent than left ventricle dilatation. The long-term consequences of right ventricular dilatation, clinical consequences, and association with pulmonary vasculopathy need to be further determined.

scholarly journals Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Vanessa Araujo Gomes Santaterra ◽  
Maiara Marx Luz Fiusa ◽  
Bidossessi Wilfried Hounkpe ◽  
Francine Chenou ◽  
Wouitchekpo Vincent Tonasse ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Healthy Volunteers ◽  
Sickle Cell ◽  
Endothelial Barrier ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Experimental Conditions ◽  
Cell Monolayers ◽  
Junction Protein

Free extracellular heme has been shown to activate several compartments of innate immunity, acting as a danger-associated molecular pattern (DAMP) in hemolytic diseases. Although localized endothelial barrier (EB) disruption is an important part of inflammation that allows circulating leukocytes to reach inflamed tissues, non-localized/deregulated disruption of the EB can lead to widespread microvascular hyperpermeability and secondary tissue damage. In mouse models of sickle cell disease (SCD), EB disruption has been associated with the development of a form of acute lung injury that closely resembles acute chest syndrome (ACS), and that can be elicited by acute heme infusion. Here we explored the effect of heme on EB integrity using human endothelial cell monolayers, in experimental conditions that include elements that more closely resemble in vivo conditions. EB integrity was assessed by electric cell-substrate impedance sensing in the presence of varying concentrations of heme and sera from SCD patients or healthy volunteers. Heme caused a dose-dependent decrease of the electrical resistance of cell monolayers, consistent with EB disruption, which was confirmed by staining of junction protein VE-cadherin. In addition, sera from SCD patients, but not from healthy volunteers, were also capable to induce EB disruption. Interestingly, these effects were not associated with total heme levels in serum. However, when heme was added to sera from SCD patients, but not from healthy volunteers, EB disruption could be elicited, and this effect was associated with hemopexin serum levels. Together our in vitro studies provide additional support to the concept of heme as a DAMP in hemolytic conditions.

scholarly journals Mineral Content and Antisickling Activity of Annona senegalensis, Alchornea cordifolia and Vigna unguiculata Used in the Management of Sickle Cell Disease in the Kwilu Province (Congo, DR)

2020 ◽  
pp. 18-27
Author(s):  
Jules M. Kitadi ◽  
Clément L. Inkoto ◽  
Emmanuel M. Lengbiye ◽  
Damien S. T. Tshibangu ◽  
Dorothée D. Tshilanda ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Mineral Composition ◽  
Sickle Cell ◽  
Mineral Elements ◽  
Spectrometric Method ◽  
Spectrometric Analysis ◽  
Composition Analysis ◽  
Cell Disease ◽  
Republic Of The Congo

Aims: To determine the mineral composition of some plants (Annona senegalensis Pers., Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg. and Vigna unguiculate (L.) Walp.) used in the management of sickle cell disease by traditional practitioners in Kwilu province and to evaluate their antisickling activity in vitro.  Study Design: Plant collection in the Kwilu province, sample preparation,  antisickling tests and fluorescence spectrometric analysis. Place and Duration of Study: This work was performed at the Faculty of Science, University of Kinshasa, Congo DR, from October 2016 to January 2018. Methodology: These three plants were harvested in the province of Kwilu in Democratic Republic of the Congo. The mineral composition analysis was carried out using the fluorescence spectrometric method while the in vitro antisickling activity was evaluate using Emmel and hemolysis tests. Results: Twenty three mineral elements were identified in each of these three plants: Potassium (K), Phosphorus (P), Calcium (Ca), Sodium (Na), Magnesium (Mg), Sulphur (S), Chlorine (Cl) and trace elements as: Aluminum (Al), Silicon (Si), Vanadium (V), Chromium (Cr), Manganese (Mn), Iron (Fe), Nickel (Ni), Copper (Cu), Zinc (Zn), Selenium (Se), Brome (Br), Molybdenum (Mo), Tin (Sn), Iodine (I), Barium (Ba) and Lead (Pb). Annona senegalensis Pers., Alchornea cordifolia (Schumach. & Thonn.) Müll.Arg. and Vigna unguiculate (L.) Walp. aqueous extracts showed the capacity to prevent the sickling and the hemolysis of red blood cells. Conclusion: The obtained results confirm the antisickling activity thus justifying the use of these plants in Traditional Medicine for the management of sickle cell disease. The presence of some mineral elements like Fe, Zn, Mg and Se are useful for sickle cell disease patients.

scholarly journals Sodium phenyl butyrate downregulates endothelin-1 expression in cultured human endothelial cells: Relevance to sickle-cell disease

2007 ◽  
Vol 82 (5) ◽  
pp. 357-362 ◽  
Author(s):  
Marie-Hélène Odièvre ◽  
Manuel Brun ◽  
Rajagopal Krishnamoorthy ◽  
Claudine Lapouméroulie ◽  
Jacques Elion
Keyword(s):  
Endothelial Cells ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Human Endothelial Cells ◽  
Endothelin 1

Abstract 345: Syzygium Jambos: A Potential Therapeutic Approach to Treat the Vascular and Hematological Complications of Sickle Cell Disease

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Analaura Santiago-Perez ◽  
Yaritza Inostroza-Nieves ◽  
Daniel Gil de la Madrid ◽  
Isamar Alicea ◽  
Christopher Vega ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Therapeutic Approach ◽  
Thrombus Formation ◽  
Critical Role ◽  
Antioxidant Properties ◽  
Cell Disease ◽  
Syzygium Jambos ◽  
Promising Therapeutic Approach

Protein disulfide isomerase (PDI) is an oxidoreductase that mediates thiol/disulfide interchange reactions and has been reported to play a critical role in thrombus formation following vascular injury. PDI has also been shown to regulate leukocyte adherence to the endothelium and nitric oxide delivery. We recently reported that PDI is present at high levels and regulates erythrocyte homeostasis and Gardos Channel activity in humans with Sickle Cell Disease (SCD). Thus, PDI inhibition has been proposed as a promising therapeutic approach to ameliorate both the vascular and hematological complications of SCD. Syzygium jambos (S. jambos) is purported to have anti-inflammatory and antioxidant properties. However, the regulation of PDI activity by S. jambos has not been studied. We studied in vitro PDI activity in the presence of the S. jambos aqueous leaf extract using a PDI insulin turbidity assay. We observed significant reductions in PDI activity at 25 μg/mL (66.0 ± 9.7%, p<0.01, n=3), 50 μg/mL (83.3 ± 6.0%, p<0.01, n=3), and 100 μg/mL (91.6 ± 11.5%, p<0.01, n=3). S. jambos extract showed a dose-dependent anti-PDI activity with an IC50 of 14.40 μg/mL. We then tested the effects of S. jambos on endothelin-1 (ET-1)-stimulated PDI activity in human endothelial cells. Using a fluorescence based PDI activity assay, we observed that ET-1 increased PDI activity (1.7 ± 0.7 folds, n=3) that was dose-dependently blocked by S. jambos extract. In addition, we observed that ET-1 stimulated ex vivo human polymorphic nucleated (PMN) leukocyte migration toward the endothelial cells that was likewise dose-dependently blocked by S. jambos extract. (p<0.01, n=3). We also quantified the levels of reactive oxygen species (ROS) production in ET-1 treated endothelial cells. ET-1 stimulation significantly increased ROS levels [3 fold] when compared to vehicle treatment (p<0.05, n=3). S. jambos extract reduced ET-1 stimulated ROS to baseline levels (p<0.05, n=3). Our results suggest that S. Jambos may represent a novel pharmacological approach to treat complications of SCD.

scholarly journals In vivo survival studies of 51Cr-labeled methyl acetimidate treated erythrocytes in patients with sickle cell disease

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 1041-1047 ◽  
Author(s):  
TG Gabuzda ◽  
TL Chao ◽  
MR Berenfeld ◽  
T Gelbart
Keyword(s):  
Sickle Cell Disease ◽  
Survival Time ◽  
Sickle Cell ◽  
Clinical Testing ◽  
Cell Disease ◽  
Show Evidence ◽  
Survival Studies ◽  
Circulating Antibody

Abstract Studies of the survival time of 51Cr labeled erythrocytes treated in vitro with methyl acetimidate (MAI) were conducted in 13 patients with sickle cell disease in order to assess the suitability of this antisickling agent for more extensive clinical testing. In comparison with previously measured control values (average t1/2 8.4 +/- 1.1 days a), the survival time of the treated erythrocytes in 10 of the patients who were not transfused was initially prolonged (average t1/2 24.4 +/- 4.6 days). However, 5 of the 13 patients studied developed circulating antibody against the MAI treated erythrocytes, markedly reducing the survival time of MAI treated erythrocytes in subsequent studies. Two patients, each challenged 3 times with infused MAI treated erythrocytes, failed to show evidence of antibody production, suggesting that not all subjects become immunized even after repeated exposure. In spite of many other promising properties of MAI as an antisickling agent of potential value, consideration of its use in further clinical testing must depend on successful avoidance of immunization in patients receiving infusions of treated erythrocytes.

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