Human vascular adhesion protein 1 (VAP-1) is a unique sialoglycoprotein that mediates carbohydrate-dependent binding of lymphocytes to endothelial cells.
Marko Salmi,Sirpa Jalkanen +1 more
TLDR
VAP-1 naturally exists as a 170-kD sialoglycoprotein that uses sialic acid residues to interact with its counter-receptors on lymphocytes under nonstatic conditions and extends the role of carbohydrate- mediated binding in lymphocyte-endothelial cell interactions beyond the known selectins.Abstract:
The regulated interactions of leukocytes with vascular endothelial cells are crucial in controlling leukocyte traffic between blood and tissues. Vascular adhesion protein-1 (VAP-1) is a novel, human endothelial cell molecule that mediates tissue-selective lymphocyte binding. Two species (90 and 170 kD) of VAP-1 exist in lymphoid tissues. Glycosidase digestions revealed that the mature 170-kD form of VAP-1 expressed on the lumenal surfaces of vessels is a heavily sialylated glycoprotein. The sialic acids are indispensable for the function of VAP-1, since the desialylated form of VAP-1 no longer mediates lymphocyte binding. We also show that L-selectin is not required for binding of activated lymphocytes to VAP-1 under conditions of shear stress. The 90-kD form of VAP-1 was only seen in an organ culture model, and may represent a monomeric or proteolytic form of the larger species. These data indicate that L-selectin negative lymphocytes can bind to tonsillar venules via the VAP- 1-mediated pathway. Moreover, our findings extend the role of carbohydrate-mediated binding in lymphocyte-endothelial cell interactions beyond the known selectins. In conclusion, VAP-1 naturally exists as a 170-kD sialoglycoprotein that uses sialic acid residues to interact with its counter-receptors on lymphocytes under nonstatic conditions.read more
Citations
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Molecular Mechanisms of Lymphocyte Homing to Peripheral Lymph Nodes
TL;DR: The results suggest that lymphocyte– HEV interactions within PLNs are almost exclusively initiated by L-selectin followed by a G protein–coupled lymphocyte-specific activation event and activation-induced engagement of LFA-1, which constitute a unique adhesion cascade that dictates the specificity of lymphocyte homing to PLNs.
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Cloning of Vascular Adhesion Protein 1 Reveals a Novel Multifunctional Adhesion Molecule
TL;DR: It is proposed that VAP-1 is a novel type of adhesion molecule with dual function, with the appropriate glycosylation and in the correct inflammatory setting, its expression on the lumenal endothelial cell surface allows it to mediate lymphocyte adhesion and to function as an adhesion receptor involved in lymphocyte recirculation.
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Immunology of the tonsils
Marta E Perry,Anthony Whyte +1 more
TL;DR: The unique nature of the various human tonsils reveals that they are capable of a variety of complex immunological functions, as discussed by Marta Perry and Anthony Whyte.
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The physiology of leukocyte recruitment: an in vivo perspective.
TL;DR: The mechanisms of leukocyte recruitment have been studied extensively in vitro and have shed light on the basic molecular structure-function relationship of adhesion and signaling molecules involved in this essential immune response, and physiological results that might not have been predicted from in vitro are highlighted.
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Recruitment of lymphocytes to the human liver
TL;DR: The expression and function of a newly defined adhesion protein, (VAP‐1), are discussed, and it is suggested that the unique functions of this protein may provide therapeutic potential for the treatment of liver disease.
References
More filters
Journal ArticleDOI
Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm
Journal ArticleDOI
Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity
Journal ArticleDOI
Leukocyte-endothelial adhesion molecules.
Timothy M. Carlos,John M. Harlan +1 more
TL;DR: Investigations have progressed from the early descriptions by intravital microscopy and histology, to functional and immunologic characterization of adhesion molecules, and now to the development of genetically deficient animals and the first phase I trial of "anti-adhesion" therapy in humans.
Journal ArticleDOI
alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow.
C. Berlin,Robert F. Bargatze,Robert F. Bargatze,James Campbell,U H von Andrian,M.C Szabo,Sharon R. Hasslen,Robert D. Nelson,Ellen L. Berg,Stanley L. Erlandsen,Eugene C. Butcher +10 more
TL;DR: In this paper, the alpha 4 integrin ligands MAdCAM and VCAM-1 support loose reversible interactions including rolling, as well as rapid sticking and arrest that is favored following integrin activation.
Journal ArticleDOI
Selectin ligands
TL;DR: This review analyzes the matter and suggests the hypothesis that at least some of the specificity of the selectins may involve recognition of "clustered saccharide patches."
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