title: An antibody to the sixth Ig-like domain of VCAM-1 inhibits leukocyte transendothelial migration without affecting adhesion.
abstract: VCAM-1 plays a key role in leukocyte trafficking during inflammatory responses. However, molecular mechanisms underlying this function have not been clearly elucidated. In this study, using phage display technology, we developed a rabbit/human chimeric VCAM-1 Ab, termed VCAM-1 domain 6 (VCAM-1-D6), which specifically recognizes aa 511-599 within the sixth Ig-like domain. We report that the VCAM-1-D6 Ab blocked U937 cell transmigration across activated HUVECs but did not alter adhesion of U937 cells to the HUVECs. We also demonstrate that VCAM-1-D6 does not alter TNF-α-stimulated endothelial cell chemokine or cytokine production. Furthermore, through in vivo efficacy testing using a mouse islet allograft model, we demonstrate that VCAM-1-D6 significantly alleviates allograft rejection by blocking leukocyte infiltration to the grafted islets. Taken together, our results suggest that the VCAM-1-D6 Ab may block VCAM-1-mediated inflammation and could be a useful tool in treating inflammatory diseases.
authors.affiliation: Cancer Research Institute, Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul 110-799, Korea.
authors.forename: Sukmook
authors.initials: S
authors.lastname: Lee
authors.forename: Il-Hee
authors.initials: IH
authors.lastname: Yoon
authors.forename: Aerin
authors.initials: A
authors.lastname: Yoon
authors.forename: Joan M
authors.initials: JM
authors.lastname: Cook-Mills
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Junho
authors.initials: J
authors.lastname: Chung
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology*; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D017434:Protein Structure, Tertiary / Q000235:genetics; D011817:Rabbits; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D019010:Vascular Cell Adhesion Molecule-1