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.

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 Interleukin-4 (IL-4) and IL-13 bind to a shared heterodimeric complex on endothelial cells mediating vascular cell adhesion molecule-1 induction in the absence of the common gamma chain

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4286-4295 ◽  
Author(s):  
B Schnyder ◽  
S Lugli ◽  
N Feng ◽  
H Etter ◽  
RA Lutz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Interleukin 4 ◽  
Vascular Cell Adhesion ◽  
Gamma Chain ◽  
Vascular Cell ◽  
The Common ◽  
Cell Adhesion Molecule 1

Interleukin-4 (IL-4) and IL-13 exert similar, nonadditive effects on endothelial cells, inducing vascular cell adhesion molecule-1 (VCAM-1) expression and subsequent transmigration of eosinophils. The receptor for IL-4 and IL-13 was described as a shared heteromultimeric complex in which the common gamma-chain (gamma c) subunit was essential for activity. Endothelial cell bound both cytokines with high affinity; by flow cytofluorometry and reverse transcription-polymerase chain reaction (RT-PCR), they expressed IL-4 receptor alpha (IL-4R alpha) but did not express the gamma c of the IL-2R. Radioligand cross-linking experiments followed by immunoprecipitation with the monoclonal antibody (MoAb) S697 to the IL-4R alpha showed IL-4-specific binding at 130 kD, the IL-4R alpha, and to a minor extent to a double band coimmunoprecipitated at 65 to 75 kD. [125 I]IL-13 bound predominantly to the 65- to 75- kD band and with a trace amount of binding at 130 kD. However, no ligand-cross-linked receptor was precipitated by the MoAb S697, indicating a cognate novel IL-13-binding subunit. Excess unlabeled IL-4 completely displaced IL-13 binding. Similarly, nonsignaling IL-4 (Y124D)-mutant abolished IL-4- and IL-13-mediated signal transduction. Unlabeled IL-13 competed successfully for IL-4 binding at 65 to 75 kD but was unable to completely displace Il-4 from its binding to the IL-4R alpha. The MoAb TUGh4, specific for the gamma c, failed to precipitate ligand-cross-linked IL-4R and IL-13R. Therefore, the subunit structure of the functional receptors for IL-4 and IL-13 on human endothelial cells does not use or require the common gamma c of the IL-2R.

Eosinophil Tethering to Interleukin-4–Activated Endothelial Cells Requires Both P-Selectin and Vascular Cell Adhesion Molecule-1

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3904-3911 ◽  
Author(s):  
Kamala D. Patel
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Interleukin 4 ◽  
Shear Stresses ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Cell Adhesion Molecule 1 ◽  
Low Shear

We examined the mechanisms used by eosinophils to tether and accumulate on interleukin-4 (IL-4)–stimulated human umbilical vein endothelial cells (HUVECs) under flow conditions. As previously reported, HUVECs treated for 24 hours with 20 ng/mL IL-4 had increased expression of P-selectin and vascular cell adhesion molecule-1 (VCAM-1) but not E-selectin. We found that eosinophils tethered and rolled on IL-4–stimulated HUVECs at physiologic shear stresses. Eosinophil rolling was quickly followed by firm adhesion. Treatment with either an anti–P-selectin monoclonal antibody (MoAb) or an anti–VCAM-1 MoAb decreased both eosinophil tethering and accumulation at 2 dyn/cm2. VCAM-1 interacts with 4-integrins expressed on eosinophils. We found that an anti–4-integrin MoAb also blocked eosinophil tethering and accumulation at 2 dyn/cm2. None of these MoAbs alone had an impact on eosinophil accumulation at lower shear stresses, but when either an anti–VCAM-1 or an anti–4-integrin MoAb was used in combination with an anti–P-selectin MoAb, all eosinophil tethering and accumulation on IL-4–stimulated HUVECs were blocked. This was true at both high and low shear stresses. These data show that both P-selectin and VCAM-1 are required to tether eosinophils at high shear stresses, but at low shear stresses these adhesion proteins can act independently to recruit eosinophils to IL-4–stimulated HUVECs.

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