title: Functions of domain 1 and 4 of vascular cell adhesion molecule-1 in alpha4 integrin-dependent adhesion under static and flow conditions are differentially regulated.
abstract: To assess the potential contributions of endothelial vascular cell adhesion molecule-1 (VCAM-1) to leukocyte adhesion under conditions of flow, we evaluated the effects of cytokine stimulation of HUVEC on primary capture, rolling, and stable adhesion of mono- and lymphoblastoid cells in a parallel-plate flow chamber. Stimulation of HUVEC with IL-1beta or IL-4 for 24 h induced surface expression of VCAM-1, consistent with published results. Using blocking mAbs to inhibit specific adhesion molecules, we found that a significant level of primary capture at wall shear stresses between 0.5 and 2.0 dynes/cm2 could be attributed to alpha4 integrin and VCAM-1. This primary adhesion under flow was most often characterized by abrupt stationary adhesion with little evidence of rolling. Studies with IL-1beta-stimulated HUVEC revealed that domain 1 of VCAM-1 was solely responsible for alpha4 integrin-dependent primary capture under flow, but both domains 1 and 4 were utilized in alpha4 integrin-dependent adhesion under static conditions. In contrast to results obtained with these cytokines alone, stimulation of HUVEC with a combination of IL-1beta and IL-4 markedly reduced alpha4/VCAM-1-dependent adhesion under flow, even though the surface levels of VCAM-1 were greater than with either cytokine alone, and alpha4/VCAM-1-dependent adhesion under static conditions was intact. These results demonstrate that distinct functional differences exist between the interactions of VCAM-1 and alpha4 integrin under static and flow conditions, and they reveal the potential for endothelial modulation of adhesion under flow without altering VCAM-1-dependent adhesion under static conditions.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Abe
authors.forename: C M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D019040:E-Selectin / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D039441:Integrin alpha4; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007739:L Cells; D051379:Mice; D015394:Molecular Structure; D019007:P-Selectin / Q000502:physiology; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019040:E-Selectin; D007375:Interleukin-1; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D039441:Integrin alpha4; D015847:Interleukin-4