scholarly journals Neutrophils and leucocyte adhesion molecules in sickle cell retinopathy

2002 ◽  
Vol 86 (6) ◽  
pp. 684-690 ◽  
Author(s):  
M K. Mathews
Keyword(s):  
Adhesion Molecules ◽  
Sickle Cell ◽  
Leucocyte Adhesion

Role of Adhesion Molecules and Vascular Endothelium in the Pathogenesis of Sickle Cell Disease

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Marilyn J. Telen
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Adhesion Molecules ◽  
Sickle Cell ◽  
Vascular Endothelium ◽  
Blood Cells ◽  
Cell Disease ◽  
Adhesive Interactions ◽  
Lines Of Evidence

AbstractA number of lines of evidence now support the hypothesis that vaso-occlusion and several of the sequelae of sickle cell disease (SCD) arise, at least in part, from adhesive interactions of sickle red blood cells, leukocytes, and the endothelium. Both experimental and genetic evidence provide support for the importance of these interactions. It is likely that future therapies for SCD might target one or more of these interactions.

Hydroxyurea corrects the dysregulated L-selectin expression and increased H2O2 production of polymorphonuclear neutrophils from patients with sickle cell anemia

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2297-2303 ◽  
Author(s):  
Malika Benkerrou ◽  
Charlotte Delarche ◽  
Lamia Brahimi ◽  
Michèle Fay ◽  
Etienne Vilmer ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Sickle Cell ◽  
Adhesion Molecule ◽  
Sickle Cell Anemia ◽  
Plasma Levels ◽  
Polymorphonuclear Neutrophil ◽  
H2o2 Production ◽  
Soluble Adhesion Molecules ◽  
Hydroxyurea Treatment ◽  
History Of

Impaired polymorphonuclear neutrophil (PMN) functions during sickle cell anemia (SCA) may have a pathogenic role in the onset of vasoocclusive events. We used flow cytometry to study, in whole blood, the adhesion molecule expression and respiratory burst of PMNs from children with SCA. Three different clinical groups were studied: (1) patients with no history of vasoocclusive events (n = 15); (2) patients with a history of vasoocclusive events (n = 17); and (3) patients receiving hydroxyurea therapy for severe vasoocclusive events (n = 9). Unstimulated PMNs showed decreased L selectin expression and increased H2O2 production whatever the severity of the disease, reflecting PMN activation. This could contribute to endothelial activation reflected by abnormal plasma levels of soluble adhesion molecules (soluble intercellular adhesion molecule-1, sE selectin, and sL selectin). After stimulation with bacterial N-formyl peptides (N-formyl-methionyl-leucyl-phenylalanine [fMLP]), PMNs from untreated patients with a history of vasoocclusive events showed dysregulated L selectin shedding and increased H2O2 production. Furthermore, in these patients, tumor necrosis factor priming followed by fMLP stimulation induced an H2O2 production significantly higher than in the other patient groups and controls. These impairments could immobilize PMNs on the endothelium, thereby inducing reduced blood flow and fostering microvascular occlusion and vascular damage. In contrast, children treated with hydroxyurea showed near-normal basal and poststimulation H2O2 production as well as normal L selectin shedding after stimulation but no change in plasma levels of soluble adhesion molecules. To our knowledge, this is the first report showing major qualitative changes of PMN abnormalities upon hydroxyurea treatment in SCA patients. This strongly suggests that PMNs are a primary target of this drug.

Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens

1991 ◽  
Vol 48 (4) ◽  
pp. 502-510 ◽  
Author(s):  
Marie C. Favrot ◽  
Valérie Combaret ◽  
Evelyne Goillot ◽  
Eric Tabone ◽  
Eric Bouffet ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Leucocyte Adhesion

Effect of Hydroxyurea Treatment on In Vitro Adhesion of Sickle Erythrocytes to Sickle Leukocyte Subpopulations.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 362-362
Author(s):  
Eileen M. Finnegan ◽  
Aslihan Turhan ◽  
Jennifer Gaines ◽  
David E. Golan ◽  
Gilda Barabino
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
T Cell ◽  
Sickle Cell Disease ◽  
Adhesion Molecules ◽  
Sickle Cell ◽  
Cell Disease ◽  
Tnf Α ◽  
Adhesive Interactions ◽  
Cell Cell

Abstract Microvascular vaso-occlusion in sickle cell disease is thought to involve adhesive interactions among erythrocytes (RBCs), leukocytes and vascular endothelial cells. Recent studies have demonstrated the presence of a significant inflammatory response in sickle cell disease, including changes in the cell surface adhesion molecules that mediate cell-cell interactions in the microvasculature. In this study, we used a parallel-plate flow chamber assay to determine the subpopulations of leukocytes that are involved in sickle leukocyte-RBC interactions. We also studied the effect of treatment with hydroxyurea (HU) on these adhesive interactions. Populations of monocytes, neutrophils (PMNs) and T cells were isolated by negative selection from the peripheral blood of untreated patients with sickle cell disease (SS), sickle patients receiving HU (SS-HU), and healthy control subjects (AA). Adhesive interactions involving these leukocyte subpopulations, human umbilical vein endothelial cells (HUVECs) pretreated with tumor necrosis factor-α (TNF-α ), and autologous RBCs were measured under a shear stress of 1 dyne/cm2. Compared to the corresponding cell populations from AA individuals, PMNs, monocytes, and T cells from SS individuals were significantly more adherent to TNF-α-treated HUVECs (774±59 vs. 502±27 cells/mm2, p=0.001; 533±66 vs. 348±36 cells/mm2, p=0.024; and 470±75 vs. 227±26 cells/mm2, p=0.009, respectively). HU therapy significantly decreased the adhesion of SS PMNs to HUVECs (774±59 cells/mm2 for SS vs. 604±36 for SS-HU, p=0.025). Compared to adherent AA leukocytes, adherent SS leukocytes exhibited greater participation in adhesive interactions with autologous RBCs (41±3% for SS vs. 27±3% for AA, p=0.002), and HU treatment decreased the fraction of leukocytes that captured autologous RBCs to the control level (29±3% for SS-HU, p=0.006 vs. SS). Compared to adherent PMNs from SS individuals, adherent PMNs from SS-HU individuals showed significantly reduced participation in the capture of RBCs (53±6% for SS vs. 35±5% for SS-HU, p=0.021). Although adherent T cells from SS individuals participated significantly more in RBC capture than adherent T cells from AA individuals (28±5% for SS vs. 10±2% for AA, p=0.007), HU therapy did not have a significant effect on this parameter (21±5% for SS-HU, p=0.373). Compared to AA leukocytes, SS leukocytes captured more RBCs per participating adherent leukocyte (2.8±0.2 vs. 1.9±0.1 RBCs/cell, p=0.001). HU therapy reduced the number of RBCs captured per PMN but not the number captured per T cell. Compared to AA T cells, SS T cells captured adherent RBCs for a significantly longer period of time (51±9 vs. 26±6 seconds, p=0.035). Our data suggest that sickle neutrophils, monocytes and T cells may all be involved in adhesive interactions with sickle RBCs. PMN-RBC and monocyte-RBC interactions appear to be more numerous than T cell-RBC interactions, although T cell-RBC interactions may be stronger. HU therapy appears to target PMN-RBC and monocyte-RBC interactions preferentially. Future studies will focus on the role of particular adhesion molecules in mediating these interactions and on the potential for therapeutic interventions targeting cell-cell adhesion.

Hydroxyurea Therapy Increases Expression of BCAM/LU and Adhesion to Laminin in Children with Sickle Cell Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4806-4806
Author(s):  
Clarissa E Johnson ◽  
Marilyn J. Telen
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Sickle Cell Disease ◽  
Adhesion Molecules ◽  
Sickle Cell ◽  
Adhesion Molecule ◽  
Extracellular Matrix Protein ◽  
Published Data ◽  
Adhesion Molecule Expression ◽  
Cell Disease

Abstract Vaso-occlusion is the major cause of morbidity and mortality in sickle cell disease. The tendency of red blood cells (RBCs) to adhere to extracellular matrix molecules and the vascular endothelium is believed to be a significant contributor to the vaso-occlusive process. Some published studies have shown that hydroxyurea decreases sickle (SS) RBC adhesion to some ligands, although the mechanism by which this occurs is not completely understood. SS RBCs demonstrate increased expression of several adhesion molecules, especially BCAM/LU, and also conserve functional signaling pathways that are associated with upregulation of adhesion. BCAM/LU mediates adhesion to the extracellular matrix protein laminin. We hypothesized that patients responsive to hydroxyurea (HU) therapy would exhibit reduced adhesion to laminin as well as a decrease in adhesion molecule expression. Our subjects included patients with Hb SS between the ages of 5 to 18. They were divided into three groups: children not receiving HU therapy (n = 3); children receiving HU therapy for over 6 months (n = 5), and children initially not receiving HU but who were initiating therapy at the time of study enrollment (n = 5). Adhesion to laminin was examined using a graduated height flow chamber to quantitate the adhesion of SS RBCs. Expression of adhesion molecules was analyzed by western blot and densitometry, using monoclonal antibody to BCAM/LU. We found that HU therapy was associated with significantly increased expression of BCAM/LU (HU: 145.8 ± 14.0 SEM; no HU: 60.8 ± 11.0 SEM densitometry units, p = .0014). This somewhat unexpected finding confirms results published earlier this year by Odievre et al. (2008). Adhesion to laminin was also increased for patients on HU (HU: 9.3 ± 5.9; no HU: .3 ± .3, p=.2), although this increase was not significant, given the variability in adhesion seen among patients and the small number of subjects. Nevertheless, the increase in adhesion corresponded to the increase in BCAM/LU expression. In contrast, adhesion to endothelial cells was decreased, although not significantly, in patients on HU (HU: 38.1 ± 38; no HU: 127.2 ± 122.5, p=.6). Our findings thus confirm earlier published data showing that HU increases the expression of BCAM/LU measured by flow cytometry and further shows that this increased expression is associated with increased adhesion to laminin but not to endothelial cells. Potential mechanisms by which HU affects adhesion molecule expression and activity merit further investigation, as does the physiologic role of these alterations. Comparison of results from patient-matched pre-treatment and post-treatment samples should also help define the effects of HU. Figure Figure

Increased Circulating Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor (sLOX-1) and Increased Endothelial Cell Expression of LOX-1 in Sickle Cell Disease (SCD): A Novel Marker for SCD Vasculopathy?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 246-246
Author(s):  
Mingyi Chen ◽  
Xin Lin ◽  
Hannah Archibald ◽  
Ted Wun ◽  
Ralph Green
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Sickle Cell ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Density Lipoprotein Receptor ◽  
Enhanced Expression

Abstract Abstract 246 Introduction: Inflammation and abnormal adhesion of sickle red blood cells (RBCs), leukocytes and platelets to the vascular endothelium are postulated to play a central role in the pathogenesis of vaculopathy associated with sickle cell disease (SCD). Dysfunctional endothelial cells in the SCD vaso-occlusive process display vasoconstriction, proinflammatory and prothrombotic changes. Sickle RBCs may damage or activate the endothelium via enhanced expression of cell surface adhesion molecules such as vascular cell adhesion molecule (VCAM), intercellular adhesion molecules (ICAM), platelet endothelial cellular adhesion marker (PECAM), E- selectin, and P-selectin. In addition, SCD modulates high levels of circulating soluble adhesion molecules especially during the sickle cell crisis. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is an endothelial cell receptor for oxidized low-density lipoprotein. The enhanced expression of LOX-1 in endothelial cells has been identified in a variety of pathologic conditions including atherosclerosis, diabetic vasculopathy, hyperlipidemia and inflammation. The purpose of this study is to investigate changes in the expression of LOX-1 and its potential role in the pathogenesis of SCD vasculopathy. Methods: Using real time quantitative PCR, we analyzed LOX-1 gene expression in cultured human coronary endothelial cells (HCEC) following static incubation with sickle RBCs. We also measured circulating soluble LOX-1 (sLOX-1) concentrations by sandwich ELISA assay in SCD patient plasma. The statistical analysis was performed using Student's t-test. Results: LOX-1 gene expression in HCEC was significantly increased by incubation with sickle RBCs compared with normal RBCs. Upregulation was detected after 1 hour of incubation, and reached a peak after 6 hours. We studied 48 SCD (hemoglobin SS) patients (26 female, 22 male); vs 17 healthy (hemoglobin AA) control subjects (12 female, 5 male). The SCD cohort comprised pediatric and adult patients in steady-state (33 patients) and vaso-occlusive crisis (VOC; 15 patients). The concentration of circulating sLOX-1 protein in plasma of SCD patients (mean: 3.05±2.53 ng/mL; range 0.30 – 11.30 ng/mL) was significantly higher (p=0.0046) than in control healthy subjects (mean: 1.27±0.81 ng/mL). In the 15 SCD patients with VOC, sLOX-1 concentrations were higher, (mean: 3.65±2.40 ng/mL). Conclusions: Our study reveals that LOX-1 gene expression in endothelial cells is upregulated by incubation with SCD erythrocytes. Baseline circulating sLOX-1 levels are elevated in SCD patients compared with healthy controls. sLOX-1 levels are further elevated in VOC. Enhanced LOX-1 expression in endothelial cells may play a role in the pathophysiology of SCD vasculopathy. Studies of sLOX-1 in SCD may provide new insights into risk stratification, and may lead to novel therapeutic strategies for sickle cell patients with acute vascular complications. Disclosures: Green: Emisphere - Consultancy: Consultancy; Teva Pharmaceuticals - expert testimony: Consultancy.

scholarly journals Arginase levels and their association with Th17-related cytokines, soluble adhesion molecules (sICAM-1 and sVCAM-1) and hemolysis markers among steady-state sickle cell anemia patients

2010 ◽  
Vol 89 (9) ◽  
pp. 877-882 ◽  
Author(s):  
Wendell Vilas-Boas ◽  
Bruno A. V. Cerqueira ◽  
Angela M. D. Zanette ◽  
Mitermayer G. Reis ◽  
Manoel Barral-Netto ◽  
...  
Keyword(s):  
Steady State ◽  
Adhesion Molecules ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Soluble Adhesion Molecules

scholarly journals Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration

Diabetologia ◽  
1997 ◽  
Vol 40 (10) ◽  
pp. 1166-1171 ◽  
Author(s):  
J. A. Olson ◽  
C. M. Whitelaw ◽  
K. C. McHardy ◽  
D. W. M. Pearson ◽  
J. V. Forrester
Keyword(s):  
Diabetic Retinopathy ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Adhesion Molecules ◽  
Endothelial Cell Migration ◽  
Capillary Endothelial Cell ◽  
Leucocyte Adhesion ◽  
Retinal Capillary

scholarly journals Decreased sickle red blood cell adhesion to laminin by hydroxyurea is associated with inhibition of Lu/BCAM protein phosphorylation

Blood ◽  
2010 ◽  
Vol 116 (12) ◽  
pp. 2152-2159 ◽  
Author(s):  
Pablo Bartolucci ◽  
Vicky Chaar ◽  
Julien Picot ◽  
Dora Bachir ◽  
Anoosha Habibi ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Adhesion Molecules ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cell Disease ◽  
Hydroxyurea Treatment

Abstract Sickle cell disease is characterized by painful vaso-occlusive crises during which abnormal interactions between erythroid adhesion molecules and vessel-wall proteins are thought to play a critical role. Hydroxyurea, the only drug with proven benefit in sickle cell disease, diminishes these interactions, but its mechanism of action is not fully understood. We report that, under hydroxyurea, expression of the unique erythroid laminin receptor Lu/BCAM was increased, but red blood cell adhesion to laminin decreased. Because Lu/BCAM phosphorylation is known to activate cell adhesion to laminin, it was evaluated and found to be dramatically lower in hydroxyurea-treated patients. Analysis of the protein kinase A pathway showed decreased intracellular levels of the upstream effector cyclic adenosine monophosphate during hydroxyurea treatment. Using a cellular model expressing recombinant Lu/BCAM, we showed that hydroxyurea led to decreased intracellular cyclic adenosine monophosphate levels and diminished Lu/BCAM phosphorylation and cell adhesion. We provide evidence that hydroxyurea could reduce abnormal sickle red blood cell adhesion to the vascular wall by regulating the activation state of adhesion molecules independently of their expression level.

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