scholarly journals Chemoattractants Induce a Rapid and Transient Upregulation of Monocyte α4 Integrin Affinity for Vascular Cell Adhesion Molecule 1 Which Mediates Arrest

2001 ◽  
Vol 193 (10) ◽  
pp. 1149-1158 ◽  
Author(s):  
Jason R. Chan ◽  
Sharon J. Hyduk ◽  
Myron I. Cybulsky
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Platelet Activating Factor ◽  
Flow Chamber ◽  
Blood Monocytes ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Stromal Cell Derived Factor

Chemoattractants and chemokines induce arrest of rolling monocytes during emigration from blood into tissues. In this study, we demonstrated that α4 integrin affinity for vascular cell adhesion molecule (VCAM)-1 was upregulated rapidly and transiently by chemoattractants and stromal cell–derived factor (SDF)-1α and mediated monocyte arrest. α4 integrin affinity changes were detected and blocked using soluble VCAM-1/Fc (sVCAM-1/Fc). In a flow cytometry assay, markedly increased sVCAM-1/Fc binding to human blood monocytes or U937 cells transfected with formyl peptide (FP) receptor was detected 30 s after FP or SDF-1α treatment and declined after 2 min. In a parallel plate flow chamber assay, FP, C5a, platelet-activating factor, or SDF-1α coimmobilized with VCAM-1 induced leukocyte arrest, which was blocked by inclusion of sVCAM-1/Fc but not soluble nonimmune immunoglobulin G in the assay buffer.

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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