Abnormal neutrophil adhesion in sickle cell anaemia and crisis: relationship to blood rheology

Boghossian, S.; Nash, Gerard B.; Ja, Dormandy; Bevan, David

doi:10.1111/j.1365-2141.1991.tb04461.x

Cited by 15 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is a growing body of data that demonstrates that PS-exposed SBRCs have an increased propensity for adhesion to microvascular endothelium (6,30,34). Similarly, an increasing body of evidence supports that the state of neutrophil activation is important and could play a role in the initiation and propagation of vasoocclusive processes in sickle cell disease (2,28). This study provides further data linking neutrophil activation to SRBC-EC adhesion.…”

Section: Discussionmentioning

confidence: 71%

“…Furthermore, Lard et al (28) have demonstrated that the basal state of activation of the neutrophils from individuals with sickle cell anemia is higher than that seen in normal controls. In addition, Boghossian et al (2) and Fadlon et al (10) have demonstrated that during sickle cell pain crisis, the neutrophil is often more adherent to vascular endothelium than during steady state. These observations suggest that varying states of neutrophil activation occur in sickle cell anemia and support the histological findings reported in this study.…”

Section: Discussionmentioning

confidence: 99%

“…During neutrophil activation, phospholipase A 2 and 5-lipoxygenase activities are increased (2,33), which results in membrane phospholipid metabolism. Of the potential products of membrane phospholipid metabolism in the human neutrophils, the 5-lipoxygenase product leukotriene B 4 is the principal product (14).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Activated neutrophil-mediated sickle red blood cell adhesion to lung vascular endothelium: role of phosphatidylserine-exposed sickle red blood cells

Haynes

Obiako²,

King³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

. Activated neutrophilmediated sickle red blood cell adhesion to lung vascular endothelium: role of phosphatidylserine-exposed sickle red blood cells. Am J Physiol Heart Circ Physiol 291: H1679 -H1685, 2006. First published May 19, 2006 doi:10.1152/ajpheart.00256.2006.-Activated neutrophils (ANs) increase sickle red blood cell (SRBC) retention/adhesion in the pulmonary circulation. This study investigates the role of neutrophil activation and SRBC retention/adhesion in the pulmonary circulation through a mechanism that involves increasing phosphatidylserine (PS) exposure on the external membrane surface of the SRBCs (PS-exposed). With the use of flow cytometry, double-labeling studies were performed with a calcium-dependent phospholipidbinding protein, annexin V-fluorescein isothiocyanate fluorescence, and the erythroid-specific marker glycophorin A to assess for the percentage of PS-exposed normal and SRBCs at baseline and after coincubation with ANs. Additional studies were performed that assessed retention/adhesion of SRBCs in the isolated rat lung using 51 Cr-labeled SRBC alone, SRBC ϩ AN, SRBC ϩ AN ϩ zileuton, and SRBC ϩ AN ϩ annexin V. Specific activities of lung and perfusate were measured, and the number of retained SRBCs per gram lung was calculated. Flow cytometry demonstrated that ANs increased the percentage of PS-exposed normal and SRBCs. The 5-lipoxygenase inhibitor zileuton attenuated AN-mediated increases in PS-exposed SRBCs and decreased SRBC retention/adherence in the lung on histological sections. Similarly, in the isolated perfused lung and in histological lung sections, retention/adherence of SRBCs cloaked with annexin V was attenuated in the presence of ANs. We conclude that ANs enhance the adhesion of SRBCs to vascular endothelium by increasing red blood cell membrane externalization of PS. Zileuton attenuation of AN-mediated SRBC PS externalization suggests that a 5-lipoxygenase product(s), secreted by the AN, plays a vital role in altering the adhesive properties of PS-exposed SRBCs to vascular endothelium. zileuton; microvascular occlusion; pulmonary circulation INCREASED SICKLE red blood cell (SRBC) adhesion to vascular endothelial cells (EC) is well documented in cell culture systems (19 -21, 23, 24, 34) and is thought to be central to vasoocclusion by the SRBC. In isolated rat lung perfused with SRBC suspensions, we have shown that the retention/adherence of SRBCs was 3.5 times greater than that seen in lung perfused with normal (hemoglobin A) human red blood cells (RBCs). In isolated perfused lung, products of activated neutrophils (ANs) further enhanced SRBC retention/adherence. This effect of ANs on RBC adhesion is attenuated when neutrophils are pretreated with a 5-lipoxygenase inhibitor (16). Whereas these in vitro results suggest the involvement of leukotriene products, the cellular mechanism involved in neutrophil-mediated increased SRBC adhesion to EC has yet to be elucidated.Adhesion molecules and their ligands on the RBC membrane surface, on EC, and in plasma have been im...

show abstract

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Activated neutrophil-mediated sickle red blood cell adhesion to lung vascular endothelium: role of phosphatidylserine-exposed sickle red blood cells

Haynes

Obiako²,

King³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…58 Moreover, sickle leukocytes have abnormal adhesion and activation. 13,19,20,[59][60][61] White counts are significantly elevated and are highly correlated with stroke in children with sickle cell anemia. 62 High white count may even cause sickle crisis.…”

Section: Discussionmentioning

confidence: 99%

Transgenic sickle mice have vascular inflammation

Belcher

Bryant

Nguyen

et al. 2003

Blood

210

187

View full text Add to dashboard Cite

Inflammation may play an essential role in vaso-occlusion in sickle cell disease. Sickle patients have high white counts and elevated levels of serum C-reactive protein (CRP), cytokines, and adhesion molecules. In addition, circulating endothelial cells, leukocytes, and platelets are activated. We examined 4 transgenic mouse models expressing human ␣-and sickle ␤-globin genes to determine if they mimic the inflammatory response seen in patients. These mouse models are designated NY-S, Berk-S Antilles , NY-S/S Antilles (NY-S ؋ Berk-S Antilles ), and Berk-S. The mean white counts were elevated 1.4-to 2.1-fold (P < .01) in the Berk-S Antilles , NY-S/S Antilles , and Berk-S mice, but not in the NY-S mice compared with controls. Serum amyloid P-component (SAP), an acute-phase response protein with 60% to 70% sequence homology to CRP, was elevated 8.5-to 12.1-fold (P < .001) in transgenic sickle mice. Similarly, serum interleukin-6 (IL-6) was elevated 1.6-to 1.9-fold (P < .05). Western blots, confirming immunohistochemical staining, showed vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), and platelet-endothelial cell adhesion molecule (PECAM) were up-regulated 3-to 5-fold (P < .05) in the lungs of sickle mice. Ribonuclease protection assays (RPAs) demonstrated VCAM mRNA also was elevated in sickle mice 1.2-to 1.4-fold (P < .01). Nuclear factor B (NF-B), a transcription factor critical for the inflammatory response, was elevated 1.9-fold (P < .006) in NY-S sickle mouse lungs. We conclude that transgenic sickle mice are good models to study vascular inflammation and the potential benefit of anti-inflammatory therapies to prevent vasoocclusion in sickle cell disease. (Blood. 2003; 101:3953-3959)

show abstract

“…21 However, contradictory results on the expression of the adhesion molecules CD11b/CD18 and L selectin at the PMN surface and on the PMN respiratory burst have been reported in patients with SCA. [22][23][24][25][26] These discrepancies could be due to the fact that most studies have involved PMNs isolated from their blood environment by means of various procedures that may alter cell responses. 27 In this study PMNs from untreated SCA children with and without a history of vasoocclusive events were analyzed in fresh whole blood to minimize procedure-related changes in surface receptor expression.…”

Section: Introductionmentioning

confidence: 99%

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

Benkerrou

Delarche

Brahimi

et al. 2002

Blood

View full text Add to dashboard Cite

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 H 2 O 2 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-methionylleucyl-phenylalanine [fMLP]), PMNs from untreated patients with a history of vasoocclusive events showed dysregulated L selectin shedding and increased H 2 O 2 production. Furthermore, in these patients, tumor necrosis factor priming followed by fMLP stimulation induced an H 2 O 2 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 H 2 O 2 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. IntroductionSickle cell anemia (SCA) results from a single point mutation that substitutes valine for glutamic acid at the sixth position in the ␤-globin chain and produces hemoglobin S (Hb S). 1,2 The basic pathophysiologic mechanism, based upon the polymerization of deoxy-Hb S and the ensuing deformation, rigidification, and fragilization of the red cells, explains the 3 hallmarks of the disease: hemolytic anemia, vasoocclusive events, and progressive functional asplenia leading to increased susceptibility to infection. Even though all SCA patients have the same biochemical defect, they show wide variability in the frequency and clinical severity of vasoocclusive crises and remain asymptomatic for long periods, indicating that additional factors must contribute to the pathophysiology of vasoocclusion. 3 Abnormal red blood cell (RBC) adhesion to the endothelium has recently been forwarded as the probable initiating event of vasoocclusion, while variations in the endothelium activation state may modulate the unpredictable occurrence of the major complications. 4 Inflammation plays a major role in this process. 5 To date, hydrox...

show abstract

Abnormal neutrophil adhesion in sickle cell anaemia and crisis: relationship to blood rheology

Cited by 15 publications

References 18 publications

Activated neutrophil-mediated sickle red blood cell adhesion to lung vascular endothelium: role of phosphatidylserine-exposed sickle red blood cells

Activated neutrophil-mediated sickle red blood cell adhesion to lung vascular endothelium: role of phosphatidylserine-exposed sickle red blood cells

Transgenic sickle mice have vascular inflammation

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

Contact Info

Product

Resources

About