title: Chemoattractants induce a rapid and transient upregulation of monocyte alpha4 integrin affinity for vascular cell adhesion molecule 1 which mediates arrest: an early step in the process of emigration.
abstract: Chemoattractants and chemokines induce arrest of rolling monocytes during emigration from blood into tissues. In this study, we demonstrated that alpha4 integrin affinity for vascular cell adhesion molecule (VCAM)-1 was upregulated rapidly and transiently by chemoattractants and stromal cell-derived factor (SDF)-1alpha and mediated monocyte arrest. alpha4 integrin affinity changes were detected and blocked using soluble VCAM-1/Fc (sVCAM-1/Fc). In a flow cytometry assay, markedly increased sVCAM-1/Fc binding to human blood monocytes or U937 cells transfected with formyl peptide (FP) receptor was detected 30 s after FP or SDF-1alpha treatment and declined after 2 min. In a parallel plate flow chamber assay, FP, C5a, platelet-activating factor, or SDF-1alpha coimmobilized with VCAM-1 induced leukocyte arrest, which was blocked by inclusion of sVCAM-1/Fc but not soluble nonimmune immunoglobulin G in the assay buffer.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto and Toronto General Research Institute, Toronto, Ontario, M5G 2C4, Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Chan
authors.forename: S J
authors.initials: SJ
authors.lastname: Hyduk
authors.forename: M I
authors.initials: MI
authors.lastname: Cybulsky
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D002448:Cell Adhesion; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D039441:Integrin alpha4; D009000:Monocytes / Q000276:immunology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D020298:U937 Cells; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D004151:Dipeptides; C097577:N-formyl-norleucyl-phenylalanine; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4