Perspectives series: cell adhesion in vascular biology. Adhesive interactions of sickle erythrocytes with endothelium.

Hebbel, Robert P.

doi:10.1172/jci119442

Cited by 154 publications

(55 citation statements)

References 2 publications

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“…Furthermore, systemic markers of inflammation such as C-reactive protein, soluble adhesion molecules, endothelin-1, and cytokines are increased in plasma during steady-state and vaso-occlusive pain crisis. 6,13,15,23,24,[46][47][48] To better understand the contribution of oxidant stress and inflammation to the pathogenesis of sickle cell disease we have interrogated the abundant and readily accessible circulating leukocyte pool using global transcriptional analysis and find that sickle cell disease evokes a highly specific transcriptional response.…”

Section: Discussionmentioning

confidence: 99%

Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease

Jison

Munson²,

Barb³

et al. 2004

Blood

200

149

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In sickle cell disease, deoxygenation of intra-erythrocytic hemoglobin S leads to hemoglobin polymerization, erythrocyte rigidity, hemolysis, and microvascular occlusion. Ischemia-reperfusion injury, plasma hemoglobin-mediated nitric oxide consumption, and free radical generation activate systemic inflammatory responses. To characterize the role of circulating leukocytes in sickle cell pathogenesis we performed global transcriptional analysis of blood mononuclear cells from 27 patients in steady-state sickle cell disease (

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Section: Discussionmentioning

confidence: 99%

Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease

Jison

Munson²,

Barb³

et al. 2004

Blood

200

149

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“…This information may be useful to develop inhibitors that block the Lu-laminin interaction and may reduce the increased adhesion of sickle red cells to laminin, which is suspected to contribute to vaso-occlusion in patients (16,17). This will be of great importance also, since Lu antigens are overexpressed in some epithelial cancer tissues (36,37) and since laminin is involved in cancer metastases (38).…”

Section: Inhibition Of Lu-laminin Binding By the Lu-fc Soluble Proteimentioning

confidence: 99%

“…Increased expression of Lu antigens on sickle red blood cells correlates with an increased adhesion to laminin (9,10), which, together with other adhesion molecules like CD36 and VLA-4, might contribute to the reinforced adhesion of the sickle red blood cells to vascular endothelium leading to vasoocclusion crisis and strokes (16,17).…”

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confidence: 99%

Characterization of the Laminin Binding Domains of the Lutheran Blood Group Glycoprotein

Nemer

Gane

Colin

et al. 2001

Journal of Biological Chemistry

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Lutheran (Lu) blood group antigens and the basal cell adhesion molecule antigen reside on two glycoproteins that belong to the Ig superfamily (IgSF) and carry five Ig-like extracellular domains. These glycoproteins act as widely expressed adhesion molecules and represent the unique receptors for laminin-10/11 in erythroid cells. Here, we report the mapping of IgSF domains responsible for binding to laminin. In plasmonic resonance surface experiments, only recombinant Lu proteins containing the N-terminal IgSF domains 1-3 were able to bind laminin-10/11 and to inhibit binding of laminin to Lu-expressing K562 cells. Mutant recombinant proteins containing only IgSF domain 1, domains 1 ؉ 2, domains 1 ؉ 3, domains 2 ؉ 3, domain 3, domain 4, domain 5, and domains 4 ؉ 5 failed to bind laminin as well as a construct containing all of the extracellular domains except domain 3. Altogether, these results indicate that IgSF domains 1-3 are involved in laminin binding and that a specific spatial arrangement of these three first domains is most probably necessary for interaction. Neither the RGD nor the N-glycosylation motifs present in IgSF domain 3 were involved in laminin binding. Lutheran (Lu)1 blood group antigens and the basal cell adhesion molecule antigen (a marker of epithelial ovarian cancers) are carried by two glycoprotein (gp) isoforms of 85 kDa (Lu) and 78 kDa (Lu(v13)) that are translated from spliceoforms of a single pre-mRNA (1, 2). The Lu gps have a wide tissue distribution with a predominant expression in the basal layer of the epithelium and the endothelium of blood vessel walls (1). Lu and Lu(v13) are type I membrane proteins of the immunoglobulin superfamily (IgSF) that share a similar extracellular domain composed of five Ig-like domains (two V-set and three C2-set) and a single transmembrane domain but differ by the presence or absence of a cytoplasmic C-terminal domain of 40 amino acids (59 versus 19, respectively) (2). The extracellular domain of Lu gps contains a potential integrin binding site in the third IgSF domain as well as five N-glycosylation consensus motifs, one in the third domain and the others in the fourth domain. The 40 C-terminal residues of the Lu gp cytoplasmic tail carry three characteristic motifs involved in protein-protein interaction, polarization to plasma membrane, and intracellular signaling pathways (3), such as (i) a proline-rich motif for potential binding of Src homology 3 domains, (ii) a dileucine motif responsible for the basolateral expression of Lu gp in polarized epithelial cells (4), and (iii) potential phosphorylation motifs. These motifs are absent in the Lu(v13) gp isoform which exhibits a nonpolarized expression in epithelial cells (4). Recent studies have shown that the C-terminal intracellular domain of Lu gps interacts with the membrane skeleton (5, 6).Interestingly, the Lu gps share a significant sequence similarity with the CD146 (MUC18) and CD166 (activated leukocyte cell adhesion molecule) adhesion molecules found in human tissues (7,8), and Lu and Lu(v...

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“…7 Features of sickle cell disease that predispose patients to endothelial damage include adhesive properties of sickle reticulocytes (promoted by adhesion proteins, von Willebrand factor, and thrombospondin), leukocyte adhesion, and biomechanical disturbances of fluid shear stresses generated by increased blood flow secondary to anemia. [8][9][10] The propensity for stroke is associated with abnormal blood flow velocity in large arteries that can be detected presymptomatically by transcranial Doppler (TCD). 11 A familial predisposition to stroke in sickle cell anemia has been suggested by the observation that the prevalence of stroke among siblings with HbSS appears to be increased.…”

Section: Introductionmentioning

confidence: 99%

Stroke risk in siblings with sickle cell anemia

Driscoll

Hurlet

Styles

et al. 2003

Blood

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Cerebrovascular disease is a common cause of morbidity in sickle cell anemia (HbSS): approximately 10% of patients have a clinical stroke before 20 years of age, and another 22% have silent infarction on magnetic resonance imaging. The phenotypic variation among patients with HbSS suggests a role for modifier genes and/or environmental influences. To assess the familial component of clinical stroke in HbSS, we estimated the prevalence of clinical stroke among all patients and among HbSS sibling pairs at 9 pediatric centers. The sample included 3425 patients with sickle cell disease who were younger than 21 years, including 2353 patients with HbSS. The stroke prevalence was 4.9% for all genotypes; 7.1% for patients with HbSS; 1.1% for patients with HbS␤ o thalassemia; 0.6% for patients with S␤ ؉ thalassemia; and 0% for patients with HbSC. In 207 sibships, more than 1 child had HbSS. There were 42 sibships in which at least 1 sibling had a stroke, and in 10 of the 42, 2 siblings had a stroke. A permutation test indicated that the number of families in which 2 children had strokes was larger than the number expected if strokes were randomly distributed among children in sibships (P ‫؍‬ .0012). There was no difference in stroke prevalence based on sex, nor was the mean age at stroke presentation significantly different between singletons and sibships with stroke. We conclude that there is a familial predisposition to stroke in HbSS. Attempts to identify genetic modifiers should be initiated with familybased studies. IntroductionCerebrovascular disease is the second leading cause of mortality and a common cause of morbidity in sickle cell anemia (HbSS): approximately 10% of patients will have a clinical stroke by age 20 years, and another 22% have evidence of silent infarction on magnetic resonance imaging (MRI). 1,2 The pathophysiology of cerebrovascular disease in sickle cell anemia may involve stenosis of large arteries of the circle of Willis, intracranial hemorrhage, and/or microvascular disease. 3,4 The histology of these vascular lesions demonstrates intimal hyperplasia and smooth muscle proliferation compatible with endothelial damage. 5 A moyamoya pattern of lenticulostriate collateral vessels develops around the areas of stenosis in about 30% of patients. 6 Patients with moyamoya also have a higher risk for recurrent stroke. 7 Features of sickle cell disease that predispose patients to endothelial damage include adhesive properties of sickle reticulocytes (promoted by adhesion proteins, von Willebrand factor, and thrombospondin), leukocyte adhesion, and biomechanical disturbances of fluid shear stresses generated by increased blood flow secondary to anemia. [8][9][10] The propensity for stroke is associated with abnormal blood flow velocity in large arteries that can be detected presymptomatically by transcranial Doppler (TCD). 11 A familial predisposition to stroke in sickle cell anemia has been suggested by the observation that the prevalence of stroke among siblings with HbSS appears to be increased. 12...

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Perspectives series: cell adhesion in vascular biology. Adhesive interactions of sickle erythrocytes with endothelium.

Cited by 154 publications

References 2 publications

Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease

Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease

Characterization of the Laminin Binding Domains of the Lutheran Blood Group Glycoprotein

Stroke risk in siblings with sickle cell anemia

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