Differential regulation of transendothelial migration of THP-1 cells by ICAM-1/LFA-1 and VCAM-1/VLA-4.
The adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expressed in atherogenic lesions are thought to regulate monocyte diapedesis. To better understand their specific roles we used function-blocking antibodies and examined in a culture model the morphology, motility, and diapedesis of THP-1 cells interacting with human coronary artery endothelial cells. The number of motile THP-1 cells was reduced only when VCAM-1 or both ICAM-1 and VCAM-1 were blocked. Blockade of ICAM-1 and VCAM-1, either separately or together, reduced to the same degree the distance that THP-1 cells traveled. Diapedesis was reduced only during the simultaneous blockade of both adhesion molecules. Blockade of either ICAM-1 or VCAM-1 inhibited pseudopodia formation, but ICAM-1 blockade induced the formation of filopodia. We suggest that the interactions of endothelial ICAM-1 and VCAM-1 with their ligands differentially regulate distinct steps of diapedesis by modulating the ratio of active and inactive forms of small GTPases such as Rho, Rac, and Cdc42.
Ronald
J A
JA
Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, Canada.
Ionescu
C V
CV
Rogers
K A
KA
Sandig
M
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001161:Arteriosclerosis / Q000276:immunology; D002460:Cell Line; D048429:Cell Size; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003599:Cytoskeleton / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1