scholarly journals CXCR4 and vascular cell adhesion molecule 1 are key chemokine/adhesion receptors in the migration of cytokine-activated T cells

2012 ◽  
Vol 64 (7) ◽  
pp. 2137-2146 ◽  
Author(s):  
Jane Bryant ◽  
David J. Ahern ◽  
Fionula M. Brennan
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Adhesion Receptors ◽  
Activated T Cells ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Cell Adhesion Molecule 1

Airway recruitment of leukocytes in mice is dependent on alpha4-integrins and vascular cell adhesion molecule-1

1997 ◽  
Vol 272 (2) ◽  
pp. L219-L229 ◽  
Author(s):  
J. E. Chin ◽  
C. A. Hatfield ◽  
G. E. Winterrowd ◽  
J. R. Brashler ◽  
S. L. Vonderfecht ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Pulmonary Inflammation ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Cell Adhesion Molecule 1

The involvement of the alpha4-integrin very late activation antigen 4 and vascular cell adhesion molecule-1 (VCAM-1) in leukocyte trafficking into the airways of ovalbumin (OA)-sensitized and OA-challenged mice was investigated using in vivo administration of anti-alpha4 monoclonal antibodies (mAb) PS/2, R1-2, and M/K-2.7 (MK2), specific for VCAM-1. VCAM-1 was upregulated on endothelial cells in lung tissue after OA inhalation. PS/2, R1-2, or MK2 significantly inhibited the recruitment of eosinophils and lymphocytes into the bronchoalveolar lavage (BAL) fluid and decreased inflammation in the lung tissues. Escalating in vivo doses of PS/2 or MK2 increased circulating levels of rat immunoglobulin G in the plasma. The binding of phycoerytherin-labeled anti-alpha4 mAb to blood T cells from PS/2-treated mice was reduced, implying that alpha4 sites were already occupied. T cells and eosinophils in BAL fluid from mice treated with PS/2 or MK2 were phenotypically different from controls. Selective decreases of alpha4+ T cells in the BAL fluid after PS/2 or MK2 treatment were coupled with changes in CD8+, CD11a, and CD62L expression. The alpha4-integrin and VCAM-1 may have important roles in the antigen-induced recruitment of T cells and eosinophils during OA-induced airway inflammation. The data suggest that these adhesion molecules may be suitable targets for therapeutic intervention in certain conditions of pulmonary inflammation.

Costimulation via Vascular Cell Adhesion Molecule-1 Induces in T Cells Increased Responsiveness to the CD28 Counter-receptor B7

1993 ◽  
Vol 148 (1) ◽  
pp. 144-156 ◽  
Author(s):  
Nitin K. Damle ◽  
Kerry Klussman ◽  
Gina Leytze ◽  
Hans D. Ochs ◽  
Alejandro Aruffo ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Cell Adhesion Molecule 1

Loss of Kindlin-3 in LAD-III eliminates LFA-1 but not VLA-4 adhesiveness developed under shear flow conditions

Blood ◽  
2009 ◽  
Vol 114 (11) ◽  
pp. 2344-2353 ◽  
Author(s):  
Eugenia Manevich-Mendelson ◽  
Sara W. Feigelson ◽  
Ronit Pasvolsky ◽  
Memet Aker ◽  
Valentin Grabovsky ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Human Lymphocytes ◽  
Effector T Cells ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Cell Adhesion Molecule 1

Abstract Leukocyte adhesion deficiency (LAD)–III is associated with homozygous stop codon mutations in Kindlin-3, the hematopoietic member of the Kindlin family of integrin coactivators. In addition, a subgroup of LAD-III patients has a homozygous splice junction mutation in and reduced expression of the Rap-1 guanine nucleotide exchange factor, CalDAG-GEFI (CDGI). In this study, we compared the adhesive properties of the leukocyte function-associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrins in both primary and activated leukocytes derived from these 2 LAD-III subgroups. Primary lymphocytes lacking both Kindlin-3 and CDGI lost all firm T-cell receptor–stimulated LFA-1 adhesiveness, in contrast to LAD-III lymphocytes deficient in Kindlin-3 alone. Effector T cells expanded from all tested LAD-III variants expressed normal CDGI, but lacked Kindlin-3. These Kindlin-3–null effector T cells exhibited total loss of inside-out LFA-1 activation by chemokine signals as well as abrogated intrinsic LFA-1 adhesiveness. Surprisingly, VLA-4 in Kindlin-3–null resting or effector lymphocytes retained intrinsic rolling adhesions to vascular cell adhesion molecule-1 and exhibited only partial defects in chemokine-stimulated adhesiveness to vascular cell adhesion molecule-1. Deletion of the putative β1 Kindlin-3 binding site also retained VLA-4 adhesiveness. Thus, our study provides the first evidence that Kindlin-3 is more critical to LFA-1 than to VLA-4–adhesive functions in human lymphocytes.

scholarly journals Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1025
Author(s):  
Sara Pastorino ◽  
Sara Baldassari ◽  
Giorgia Ailuno ◽  
Guendalina Zuccari ◽  
Giuliana Drava ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Umbilical Vein ◽  
In Vitro Tests ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Cell Adhesion Molecule 1 ◽  
Pet Radiopharmaceuticals

Atherosclerosis is a chronic progressive disease involving inflammatory events, such as the overexpression of adhesion molecules including the endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1). VCAM-1 is rapidly overexpressed in the first stages of atherosclerosis, thus representing a promising target for early atheroma detection. Two novel Positron Emission Tomography (PET) radiopharmaceuticals (MacroP and NAMP), based on the VCAM-1-binding peptide having sequence VHPKQHRGGSKGC, were synthesized and characterized. MacroP is derived from the direct conjugation of a DOTA derivative with the peptide, while NAMP is a biotin derivative conceived to be employed in a three-step pretargeting system, involving the use of a double-chelating derivative of DOTA. The identity of the newly synthesized radiopharmaceuticals was confirmed by mass spectrometry and, after radiolabeling with 68Ga, both showed high radiochemical purity; in vitro tests on human umbilical vein endothelial cells evidenced their VCAM-1 binding ability, with higher radioactive uptake in the case of NAMP. Moreover, NAMP might also be employed in a theranostic approach in association with functionalized biotinylated nanoparticles.

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