Endothelial Lu/BCAM glycoproteins are novel ligands for red blood cell α4β1integrin: role in adhesion of sickle red blood cells to endothelial cells

Blood ◽  
2006 ◽  
Vol 109 (8) ◽  
pp. 3544-3551 ◽  
Author(s):  
Wassim El Nemer ◽  
Marie-Paule Wautier ◽  
Cécile Rahuel ◽  
Pierre Gane ◽  
Patricia Hermand ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Adhesion Molecule ◽  
Blood Cells ◽  
Cell Adhesion Molecule ◽  
Red Cells ◽  
Immunoglobulin Superfamily ◽  
Flow Conditions

Abstract The Lutheran (Lu) blood group and basal cell adhesion molecule (BCAM) antigens are both carried by 2 glycoprotein isoforms of the immunoglobulin superfamily representing receptors for the laminin α5 chain. In addition to red blood cells, Lu/BCAM proteins are highly expressed in endothelial cells. Abnormal adhesion of red blood cells to the endothelium could potentially contribute to the vaso-occlusive episodes in sickle cell disease. Considering the presence of integrin consensus-binding sites in Lu/BCAM proteins, we investigated their potential interaction with integrin α4β1, the unique integrin expressed on immature circulating sickle red cells. Using cell adhesion assays under static and flow conditions, we demonstrated that integrin α4β1 expressed on transfected cells bound to chimeric Lu-Fc protein. We showed that epinephrine-stimulated sickle cells, but not control red cells, adhered to Lu-Fc via integrin α4β1 under flow conditions. Antibody-mediated activation of integrin α4β1 induced adhesion of sickle red cells to primary human umbilical vein endothelial cells; this adhesion was inhibited by soluble Lu-Fc and vascular cell adhesion molecule-1 (VCAM-1)–Fc proteins. This novel interaction between integrin α4β1 in sickle red cells and endothelial Lu/BCAM proteins could participate in sickle cell adhesion to endothelium and potentially play a role in vaso-occlusive episodes.

scholarly journals Neural Cell Adhesion Molecule, a New Cytoadhesion Receptor for Plasmodium falciparum-Infected Erythrocytes Capable of Aggregation

2007 ◽  
Vol 75 (7) ◽  
pp. 3516-3522 ◽  
Author(s):  
Bruno Pouvelle ◽  
Valéry Matarazzo ◽  
Christophe Jurzynski ◽  
Johannes Nemeth ◽  
Michael Ramharter ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasmodium Falciparum ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Neural Cell ◽  
Immunoglobulin Superfamily ◽  
Flow Conditions ◽  
Neural Cell Adhesion

ABSTRACT The cytoadhesion of Plasmodium falciparum-infected erythrocytes (IEs) to the endothelial cells lining the microvasculature, clogging the microvessels of various organs, is a key event in the pathogenesis of certain severe forms of malaria, such as cerebral malaria and pulmonary edema. Studies aiming to identify possible correlations between the severity of clinical cases and the presence of particular cytoadhesion phenotypes have been largely unsuccessful. One of the possible reasons for this failure is that some of the key receptors and/or mechanisms involved have yet to be identified. By combining IE selection, cell transfection, and adhesion inhibition assays, we identified a new cytoadhesion receptor, neural cell adhesion molecule (NCAM). NCAM is a member of the immunoglobulin superfamily and has nonpolysialylated and polysialylated isoforms, the latter being rare in adults. The nonpolysialylated form is present on the surfaces of endothelial cells in the microvessels of various organs in which IE sequestration occurs. We found that multiphenotypic IEs interacted with nonpolysialylated NCAM and with another, as yet unidentified receptor. These IEs also displayed cytoadhesion in flow conditions, presenting the unique ability to form adherent macroaggregates composed of hundreds of IEs. These features may act as virulence factors, increasing the capacity of IEs to clog microvessels via receptor synergy and macroaggregate formation, thereby facilitating the pathogenesis of severe forms of malaria.

scholarly journals Alpha 4 beta 1-integrin expression on sickle reticulocytes: vascular cell adhesion molecule-1-dependent binding to endothelium

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1891-1899 ◽  
Author(s):  
RA Swerlick ◽  
JR Eckman ◽  
A Kumar ◽  
M Jeitler ◽  
TM Wick
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Sickle Cell ◽  
Adhesion Molecule ◽  
Sickle Cell Anemia ◽  
Cell Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Beta 1 Integrin ◽  
Cell Adhesion Molecule 1

Important complications in sickle cell anemia occur secondary to vascular occlusion, which is postulated to be initiated by interactions of erythrocytes with vascular endothelial cells. In patients with sickle cell anemia, up to 25% of reticulocytes express the alpha 4 beta 1-integrin complex. Furthermore, erythrocytes from patients with sickle cell anemia bind to endothelial cells activated by tumor necrosis factor alpha via (TNF alpha) via interactions between erythrocyte alpha 4 beta 1 and endothelial cell vascular cell adhesion molecule-1 (VCAM- 1). Thus, binding of alpha 4 beta 1-expressing reticulocytes to cytokine-activated endothelial cells may initiate vascular complications in sickle cell anemia and perhaps other hemolytic anemias during episodes of infection and inflammation.

A Monoclonal Antibody to Lactadherin Inhibits Sickle Red Blood Cell Adhesion to Vascular Endothelial Cells in a Plasma Milieu.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1236-1236
Author(s):  
Swapan K. Dasgupta ◽  
Prasenjit Guchhait ◽  
Anhquyen Le ◽  
Sarvari Yellapragada ◽  
Jose Lopez ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Blood Cells ◽  
Dependent Manner ◽  
Sickle Erythrocytes ◽  
Sickle Red Blood Cells

Abstract Adherence of red blood cells to the endothelium initiates vaso-occlusion in sickle cell anemia. The increased adhesiveness of sickle erythrocytes is accompanied by several changes in the lipids of the erythrocyte membrane, including increased expression of phosphatidylserine (PS). One important PS-binding protein is lactadherin (also known as milk fat globule-EGF factor 8), a 45-kDa glycoprotein containing an Arg-Gly-Asp (RGD) sequence. It is secreted by macrophages and is present in normal plasma. Lactadherin promotes phagocytosis of PS-expressing apoptotic lymphocytes and sickle red blood cells by anchoring them to integrins on macrophages. Here, we investigated the role of endogenous lactadherin in adhesion of sickle erythrocytes to the endothelium. We developed a murine monoclonal antibody to human lactadherin, called L688, and investigated its effect on the adhesion of sickle red blood cells to histamine-stimulated human umbilical vein endothelial cells under hydrodynamic flow. In three experiments using washed erythrocytes resuspended in autologous plasma from three different patients with sickle cell anemia, L688 (20 μg/ml) inhibited adhesion by 24–30% (p<0.01). Further evidence for an important role for lactadherin in sickle erythrocyte adhesion to endothelial cells was provided by the observation that exogenous lactadherin enhanced adhesion in a concentration-dependent manner. Lactadherin-mediated adhesion was also inhibited by monoclonal antibody abciximab, (c7E3, 10 μg/ml) which targets the β3 integrin subunit common to both αIIbβ3 and αVβ3. Control antibodies had no effect. Finally, the lactadherin-dependent adhesion of sickle erythrocytes to activated endothelium was inhibited by PS vesicles but not by phosphatidylcholine vesicles, confirming an important role for PS in sickle cell adhesion. Consistent with this, normal erythrocytes can be induced to adhere to stimulated HUVEC in a lactadherin-dependent manner by treatment with N-ethylmaleimide (10 mM) and calcium ionophore A23187 (4 μM) — treatment that exposes PS on the outer leaflet of the red cell membrane. Together, these results indicate that lactadherin mediates sickle cell adhesion to the endothelium by bridging PS on the erythrocytes with αVβ3 integrin on the endothelium. We propose that anemia in sickle cell disease is at least partially due to phagocytosis of lactadherin-coated sickle erythrocytes in the spleen, liver, and lymph nodes. Those erythrocytes that are not ingested immediately by macrophages will become more adhesive for endothelium. Thus, lactadherin appears to be involved both in sickle cell clearance from the circulation and in adhesion to endothelium.

scholarly journals Alpha 4 beta 1-integrin expression on sickle reticulocytes: vascular cell adhesion molecule-1-dependent binding to endothelium

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1891-1899 ◽  
Author(s):  
RA Swerlick ◽  
JR Eckman ◽  
A Kumar ◽  
M Jeitler ◽  
TM Wick
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Sickle Cell ◽  
Adhesion Molecule ◽  
Sickle Cell Anemia ◽  
Cell Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Beta 1 Integrin ◽  
Cell Adhesion Molecule 1

Abstract Important complications in sickle cell anemia occur secondary to vascular occlusion, which is postulated to be initiated by interactions of erythrocytes with vascular endothelial cells. In patients with sickle cell anemia, up to 25% of reticulocytes express the alpha 4 beta 1-integrin complex. Furthermore, erythrocytes from patients with sickle cell anemia bind to endothelial cells activated by tumor necrosis factor alpha via (TNF alpha) via interactions between erythrocyte alpha 4 beta 1 and endothelial cell vascular cell adhesion molecule-1 (VCAM- 1). Thus, binding of alpha 4 beta 1-expressing reticulocytes to cytokine-activated endothelial cells may initiate vascular complications in sickle cell anemia and perhaps other hemolytic anemias during episodes of infection and inflammation.

scholarly journals Dances with leukocytes: how tetraspanin-enriched microdomains assemble to form endothelial adhesive platforms

2008 ◽  
Vol 183 (3) ◽  
pp. 375-376 ◽  
Author(s):  
Klaus Ley ◽  
Hong Zhang
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Biology ◽  
Cell Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Immunoglobulin Superfamily ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Adhesive Surface

Rather than just providing an unstructured adhesive surface for leukocytes, cytokine-activated endothelial cells assemble preexisting tetraspanin-enriched microdomains to form endothelial adhesive platforms (EAPs) and endothelial docking structures. In this issue of the Journal of Cell Biology, Barreiro et al. (Barreiro, O., M. Zamai, M. Yáñez-Mó, E. Tejera, P. López-Romero, P.N. Monk, E. Gratton, V.R. Caiolfa, and F. Sánchez-Madrid. 2008. J. Cell Biol. 183:527–542) show how the immunoglobulin superfamily adhesion molecules intercellular adhesion molecule (ICAM)–1 and vascular cell adhesion molecule (VCAM)–1 form nanoclusters with the tetraspanins CD9 and CD151 in a physiologically relevant system. Furthermore, convincing biochemical data suggest that these structures are distinct from lipid rafts.

scholarly journals A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture.

1991 ◽  
Vol 114 (3) ◽  
pp. 557-565 ◽  
Author(s):  
K Miyake ◽  
K Medina ◽  
K Ishihara ◽  
M Kimoto ◽  
R Auerbach ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Cell Adhesion Molecule ◽  
B Lymphocyte ◽  
Murine Bone Marrow

Two new mAbs (M/K-1 and M/K-2) define an adhesion molecule expressed on stromal cell clones derived from murine bone marrow. The protein is similar in size to a human endothelial cell adhesion molecule known as VCAM-1 or INCAM110. VCAM-1 is expressed on endothelial cells in inflammatory sites and recognized by the integrin VLA-4 expressed on lymphocytes and monocytes. The new stromal cell molecule is a candidate ligand for the VLA-4 expressed on immature B lineage lymphocytes and a possible homologue of human VCAM-1. We now report additional similarities in the distribution, structure, and function of these proteins. The M/K antibodies detected large cells in normal bone marrow, as well as rare cells in other tissues. The antigen was constitutively expressed and functioned as a cell adhesion molecule on cultured murine endothelial cells. It correlated with the presence of mRNA which hybridized to a human VCAM-1 cDNA probe. Partial NH2 terminal amino acid sequencing of the murine protein revealed similarities to VCAM-1 and attachment of human lymphoma cells to murine endothelial cell lines was inhibited by the M/K antibodies. All of these observations suggest that the murine and human cell adhesion proteins may be related. The antibodies selectively interfered with B lymphocyte formation when included in long term bone marrow cultures. Moreover, they caused rapid detachment of lymphocytes from the adherent layer when added to preestablished cultures. The VCAM-like cell adhesion molecule on stromal cells and VLA-4 on lymphocyte precursors may both be important for B lymphocyte formation.

scholarly journals Anti-Inflammatory and Anti-Apoptotic Effects of Stybenpropol A on Human Umbilical Vein Endothelial Cells

2019 ◽  
Vol 20 (21) ◽  
pp. 5383 ◽  
Author(s):  
Li Zhang ◽  
Feifei Wang ◽  
Qing Zhang ◽  
Qiuming Liang ◽  
Shumei Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Umbilical Vein ◽  
Caspase 9 ◽  
Protein Levels ◽  
Tnf Α ◽  
Umbilical Vein Endothelial Cells ◽  
Cell Adhesion Molecule 1

Inflammation is a key mediator in the progression of atherosclerosis (AS). Benzoinum, a resin secreted from the bark of Styrax tonkinensis, has been widely used as a form of traditional Chinese medicine in clinical settings to enhance cardiovascular function, but the active components of the resin responsible for those pharmaceutical effects remain unclear. To better clarify these components, a new phenylpropane derivative termed stybenpropol A was isolated from benzoinum and characterized via comprehensive spectra a nalysis. We further assessed how this phenylpropane derivative affected treatment of human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α). Our results revealed that stybenpropol A reduced soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-8 (IL-8), and interleukin-1β (IL-1β) expression by ELISA, inhibited apoptosis, and accelerated nitric oxide (NO) release in TNF-α-treated HUVECs. We further found that stybenpropol A decreased VCAM-1, ICAM-1, Bax, and caspase-9 protein levels, and increased the protein levels of Bcl-2, IKK-β, and IκB-α. This study identified a new, natural phenylpropane derivative of benzoinum, and is the first to reveal its cytoprotective effects in the context of TNF-α-treated HUVECs via regulation of the NF-κB and caspase-9 signaling pathways.

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