Activated polymorphonuclear cells increase sickle red blood cell retention in lung: role of phospholipids

Haynes, Johnson; Obiako, Boniface

doi:10.1152/ajpheart.2002.282.1.h122

Cited by 25 publications

(35 citation statements)

References 60 publications

(67 reference statements)

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“…54 Although the adhesion of platelets and leukocytes to activated endothelial P-selectin [55][56][57] should have been blocked by the mAb combination that included anti-PSGL-1 mAb, it is possible that other P-selectin recognition determinants such as sulfatides 58 or glycoprotein Ib-IX-V 59 may have mediated the adhesion of nonerythroid cells to P-selectin on endothelial cells. Platelet activating factor (PAF) could have mediated the adhesion of sickle RBCs, [60][61][62] but the differences between the responses of P-selectin-deficient and wild-type mice suggest that a PAF effect was not a major one. We cannot exclude the possibility that TSP might have contributed to the changes we observed.…”

Section: Discussionmentioning

confidence: 99%

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo

Embury

Matsui²,

Ramanujam³

et al. 2004

Blood

126

121

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Microvascular occlusion in sickle cell disease can be initiated by adhesion of sickle red blood cells (RBCs) to the endothelium. Our objective in this study was to verify the relevance in vivo of our discovery that sickle RBCs adhere abnormally to endothelial P-selectin in vitro. We used computer-assisted intravital microscopy to characterize RBC flow velocity (V RBC ) in mice. We found faster V RBC of sickle RBCs in P-selectin knock-out and control mice than in sickle cell mice, which have increased endothelial cell P-selectin expression. Agonist peptide for murine protease-activated receptor-1 (PAR-1), which selectively activates mouse endothelial cells but not platelets, was used to assess the effects of endothelial cell Pselectin on microvascular flow. Suffusion of venules with this agonist stopped flow promptly in normal and sickle mice but not in P-selectin knock-out mice or in control mice pretreated with anti-P-selectin monoclonal antibody or unfractionated heparin (UFH). Agonist-induced slowing of flow was reversed rapidly by suffusion with UFH, provided flow had not already stopped. We conclude that endothelial cell P-selectin contributes to the microcirculatory abnormalities in sickle cell disease and that blocking Pselectin may be useful for preventing painful vasoocclusion in sickle cell disease. ( IntroductionMost of the morbid consequences of sickle cell disease are caused by the impairment of blood flow in the microvasculature. 1 Traditional understandings attribute the microvascular occlusion to an increase in blood viscosity caused by intraerythrocytic polymerization of deoxygenated sickle hemoglobin and the consequent sickling and rigidification of red blood cells (RBCs). 2 Kinetic considerations predict that, in the absence of preexisting intraerythrocytic polymer, impairment of blood viscosity will occur after the RBC has entered into veins too large to be occluded by rigid sickled RBCs 3 and that polymerization will occur within vessels small enough to be occluded by individual sickled RBCs only when their transit through the microcirculation is delayed.Among the factors that can prolong the transit time of sickle RBCs through the microvasculature are several polymerizationindependent processes, including vascular constriction, coagulation, inflammation, and cellular adhesion. 4 Experimental evidence supports a 2-step mechanism of vasoocclusion initiated by the binding of an adhesive subset of sickle RBCs to the vascular endothelium and completed by the logjamming of more rigid sickle RBCs behind the adherent nidus. 5 This discovery has provided an understanding of the onset of painful vasoocclusion that is lacking from detailed explications of hemoglobin S polymerization and RBC sickling and notions of systemic deoxygenation 6 and inspired a profusion of research into mechanisms of adhesion and adhesion-blocking therapies. 7,8 The expression of cytoadhesion molecules on endothelial cells isolated from the circulating blood of patients with sickle cell disease 9 and on intact endothelial c...

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Section: Discussionmentioning

confidence: 99%

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo

Embury

Matsui²,

Ramanujam³

et al. 2004

Blood

126

121

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“…Human neutrophils were isolated according to a previous report ( 56 ). All protocols utilizing human neutrophils were approved by the Medical College of Wisconsin Institutional Review Board.…”

Section: Pma-induced Hocl Formation By Human Neutrophilsmentioning

confidence: 99%

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor

Zhang¹,

Jing²,

Shi³

et al. 2013

Journal of Lipid Research

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“…The zileuton concentrations used were based on previous findings reported by Guidot et al (14), Haynes and Obiako (16), and studies performed in our laboratory demonstrating a 50% reduction of leukotriene B 4 at 2.5 M and a 95% reduction of leukotriene B4 at the 50 M in A-23187-stimulated whole blood from individuals with sickle cell anemia. The effect of zileuton on SRBC PS externalization was assessed based on a previous study (16), which demonstrated that zileuton attenuates AN mediated retention/adherence of SRBCs in isolated perfused lung.…”

Section: Specific Protocolsmentioning

confidence: 99%

“…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.…”

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confidence: 93%

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

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. 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...

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Activated polymorphonuclear cells increase sickle red blood cell retention in lung: role of phospholipids

Cited by 25 publications

References 60 publications

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor

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

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