Domains 1 and 4 of vascular cell adhesion molecule-1 (CD106) both support very late activation antigen-4 (CD49d/CD29)-dependent monocyte transendothelial migration.
We investigated the role of the 6 domain (6D) and 7 domain (7D) forms of human VCAM-1 as counter-receptors for the alpha 4 beta 1 integrin (VLA-4) in monocyte migration induced by C5a. Across Chinese hamster ovary (CHO) cell monolayers transfected with VCAM-6D or VCAM-7D, monocyte migration was not inhibited by treatment of monocytes with mAb to CD18. Addition of mAb to alpha 4 to the CD18 mAb inhibited monocyte migration by 90% across CHO VCAM-6D and CHO VCAM-7D. mAbs to domain 1 (4B9) or domain 4 (GH12) of VCAM-1 each inhibited migration across CHO VCAM-7D partially, when monocytes were also treated with anti-CD18 mAb. When the VCAM-1 mAbs were combined, migration of these monocytes across CHO VCAM-7D was further inhibited to the same degree as with mAbs to alpha 4 plus CD18. IL-1-treated human umbilical vein endothelium (HUVE) supported CD18-independent, VLA-4-mediated monocyte migration to C5a. A mAb to domain 1 of VCAM-1 almost completely inhibited the CD18-independent migration across HUVE activated with IL-1 for 2 h or 20 h, but was less inhibitory when HUVE was treated with IL-1 for 5 h. However, when mAbs to domain 1 and domain 4 were combined, CD18-independent migration was inhibited completely under all conditions tested. These results suggest that either domain 1 or domain 4 of VCAM-1 can mediate VLA-4-dependent monocyte transendothelial migration, that VLA-4 interaction with these two domains can account for all of the VLA-4-mediated migration, and that the expression of VCAM-1 variants on HUVE depends partly on the duration of IL-1 activation.
Chuluyan
H E
HE
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Osborn
L
L
Lobb
R
R
Issekutz
A C
AC
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000502:physiology*; D000939:Epitopes; D006801:Humans; D039441:Integrin alpha4; D019012:Integrin beta1; D016023:Integrins / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D010449:Peptide Mapping; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D000939:Epitopes; D019012:Integrin beta1; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4