Effect of interleukin-8 and RANTES on the Gardos channel activity in sickle human red blood cells: Role of the Duffy antigen receptor for chemokines

Durpès, Marie-Claude; Nebor, Danitza; Mesnil, Pierre Couespel du; Mougenel, Danièle; Decastel, Monique; Élion, Jacques; Hardy‐Dessources, Marie‐Dominique

doi:10.1016/j.bcmd.2010.02.001

Cited by 17 publications

(14 citation statements)

References 24 publications

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“…The RBC fraction between densities 1·076 and 1·106 (i.e. light fraction) corresponded to reticulocytes (20–30%) and discocytes (70–80%) while the RBC fraction at the bottom of the tube (density > 1·106; heavy fraction) was composed of intermediary dense cells and irreversibly sickled cells (Durpes et al , ). Each RBC fraction was washed three times in phosphate‐buffered saline + 10 mmol/l glucose (pH 7·4 at 37°C, 300 mos mol/kg H 2 O) and resuspended in autologous plasma at adjusted Hct (40%) for haemorheological analysis.…”

Section: Methodsmentioning

confidence: 99%

Haemolysis and abnormal haemorheology in sickle cell anaemia

et al. 2014

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SummaryAlthough pulmonary hypertension, leg ulcers, priapism, stroke and glomerulopathy in sickle cell anaemia (SCA) result from the adverse effects of chronic haemolysis on vascular function (haemolytic phenotype), osteoneocrosis, acute chest syndrome and painful vaso-occlusive crises are caused by abnormal vascular cell adhesion and increased blood viscosity (viscosityvaso-occlusion phenotype). However, this model with two sub-phenotypes does not take into account the haemorheological dimension. We tested the relationships between the biological parameters reflecting the haemolytic rate (haemolytic component) and red blood cell (RBC) rheological characteristics in 97 adults with SCA. No significant difference in the proportion of patients with low or high haemolytic component in the low and high blood viscosity groups was observed. The RBC elongation index (i.e. deformability) was negatively correlated with the haemolytic component. The RBC aggregates strength (i.e. RBC aggregates robustness) was negatively correlated with RBC elongation index. Sickle RBCs with high density had lower elongation index and higher aggregates strength. In conclusion, (i) the 'haemolytic' phenotype is characterized by decreased RBC deformability and increased RBC aggregates strength and (ii) the viscosityvaso-occlusive phenotype is characterized by increased RBC deformability but not always by increased blood viscosity. a-thalassaemia modulates the haemorheological properties but other factors seem to be involved.

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Section: Methodsmentioning

confidence: 99%

Haemolysis and abnormal haemorheology in sickle cell anaemia

et al. 2014

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“…In this regard, ␣4␤1 conformation and therefore its activation states could be related to the presence or absence of DARC. More recently, we have also demonstrated that IL-8 and RANTES elicit a stimulation of the deoxygenation stimulated potassium loss via the Gardos channel in Duffy-positive but not in Duffy-negative sickle RBCs (31). Altogether, these data suggest a coupling between DARC and activation processes involved in increased adhesion and dehydration that play a role in the SCA pathogenesis.…”

Section: Discussionmentioning

confidence: 58%

Activation State of α4β1 Integrin on Sickle Red Blood Cells Is Linked to the Duffy Antigen Receptor for Chemokines (DARC) Expression

Durpès

Hardy‐Dessources

Nemer

et al. 2011

Journal of Biological Chemistry

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In sickle cell anemia, reticulocytes express enhanced levels of ␣4␤1 integrin that interact mainly with vascular cell adhesion molecule-1 and fibronectin, promoting vaso-occlusion. These interactions are known to be highly sensitive to the inflammatory chemokine IL-8. The Duffy antigen receptor for chemokines (DARC) modulates the function of inflammatory processes. However, the link between ␣4␤1 activation by chemokines and DARC erythroid expression is not or poorly explored. Therefore, the capacity of ␣4␤1 to mediate Duffy-negative and Duffy-positive sickle reticulocyte (SRe) adhesion to immobilized vascular cell adhesion molecule-1 and fibronectin was evaluated. Using static adhesion assays, we found that, under basal conditions, Duffypositive SRe adhesion was 2-fold higher than that of Duffynegative SRes. Incubating the cells with IL-8 or RANTES (regulated on activation normal T cell expressed and secreted) increased Duffy-positive SRe adhesion only, whereas Mn 2؉ increased cell adhesion independently of the Duffy phenotype. Flow cytometry analyses performed with anti-␤1 and anti-␣4 antibodies, including a conformationsensitive one, in the presence or absence of IL-8, revealed that Duffy-positive and Duffy-negative SRes displayed similar erythroid ␣4␤1 expression levels, but with distinct activation states. IL-8 did not affect ␣4␤1 affinity in Duffy-positive SRes but induced its clustering as corroborated by immunofluorescence microscopy. Our results indicate that in Duffy-negative SRes ␣4␤1 integrin is constitutively expressed in a low affinity state, whereas in Duffy-positive SRes ␣4␤1 is expressed in a higher chemokine-sensitive affinity state. This activation state associated with DARC RBC expression may influence the intensity of the inflammatory responses encountered in sickle cell anemia and participate in its interindividual clinical expression variability.␣4␤1 (CD49d/CD29, VLA4), the only integrin expressed on young SRes, 3 is a multifunctional adhesion protein mediating cell attachment via different ligands, the majors being VCAM-1 and FN (1, 2). In addition to reduced deformability of sickle erythrocytes, increased red cell adhesion to endothelium has been reported (3, 4). This abnormal adhesion may profoundly influence vaso-occlusive crises, by favoring cell contacts with the microvascular and venular endothelium via the ␣4␤1/VCAM-1 and/or the ␣4␤1/FN interactions (2, 5-7). As demonstrated previously, these interactions are highly sensitive to the inflammatory chemokine IL-8 in SCA (6, 7) as in other situations (8). In addition, the implication of IL-8 in the severity of vaso-occlusive episodes has been demonstrated (9). Together, these data suggest the importance of IL-8 in vasoocclusive crises through ␣4␤1 activation (5-7, 9, 10).Red blood cells (RBCs) express the Duffy blood group antigens (Fy) (11) carried by a glycoprotein identified as the Duffy antigen receptor for chemokines (DARC) of both the CC and the CXC classes, including . Four major Duffy phenotypes are serologically identified: Fy ...

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“…[19]. CCL5 is involved in the red cell dehydration process and in inflammatory reactions [7]. The gene encoding this cytokine is home to various polymorphisms; three of them, namely g.-403G>A and g.-28C>G in the promoter and g.In1.+1T>C in the first intron, have been suggested to affect the expression of CCL5 [8].…”

Section: Discussionmentioning

confidence: 99%

“…The choice of these complications was based on the implication of CCL5 in the pathophysiology of SCA. Indeed, the activation of the Gardos channel by CCL5 causes the dehydration of red cells and therefore may aggravate the occurrence of vaso-occlusive crisis (VOC) [6,7]. Furthermore, CCL5 plays an important role in the immune response to infection.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, RANTES activates the Gardos channel via its erythrocyte receptor called Duffy antigen receptor for chemokines (DARC). The activation of this channel causes a massive loss of potassium and water, leading to the dehydration of red cells [6,7]. The human CCL5 gene spans 8.8 kb on chromosome 17 (q11.2-q12) and consists of a promoter, three exons and two introns.…”

Section: Introductionmentioning

confidence: 99%

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Frequency of three polymorphisms of the CCL5 gene (rs2107538, rs2280788 and rs2280789) and their implications for the phenotypic expression of sickle cell anemia in Tunisia

Kalai¹,

Chaouch²,

Mansour³

et al. 2013

pjp

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The pro-inflammatory context of sickle cell disease promotes the liberation of cytokines such as CCL5, encoded by a gene located on chromosome 17. Herein, the occurrence of three variations of CCL5 in sickle cell anemia (SCA) and their relations to two major complications -painful crisis and presence of infections -were investigated. 100 SCA Tunisian patients and 100 healthy subjects were included in the case control study. Then the sample of patients was divided into two groups according to the presence or absence of each complication. The polymorphisms, namely g.-403G>A, g.-28C>G and g.In1.+1T>C, were analyzed by PCR/sequencing. Our findings show the presence of eight genotypes, namely GG, GA and AA of g.-403G>A, CC, CG and GG of g.-28C>G, and TT and TC of g.In1.+1T>C. The frequencies of studied single nucleotide polymorphisms (SNPs) and haplotypes in SCA patients do not differ significantly from healthy control group results. There is also no significant association between the analyzed polymorphisms and complications as for painful crisis and presence of infections (p > 0.05). Altogether, our data support the conclusion that the three polymorphisms of CCL5, namely g.-403G>A, g.-28C>G and g.In1.+1T>C, do not seem to be involved in the clinical variability of SCA in Tunisia.

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Effect of interleukin-8 and RANTES on the Gardos channel activity in sickle human red blood cells: Role of the Duffy antigen receptor for chemokines

Cited by 17 publications

References 24 publications

Haemolysis and abnormal haemorheology in sickle cell anaemia

Haemolysis and abnormal haemorheology in sickle cell anaemia

Activation State of α4β1 Integrin on Sickle Red Blood Cells Is Linked to the Duffy Antigen Receptor for Chemokines (DARC) Expression

Frequency of three polymorphisms of the CCL5 gene (rs2107538, rs2280788 and rs2280789) and their implications for the phenotypic expression of sickle cell anemia in Tunisia

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