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.
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.
Chan
J R
JR
Department of Laboratory Medicine and Pathobiology, University of Toronto and Toronto General Research Institute, Toronto, Ontario, M5G 2C4, Canada.
Hyduk
S J
SJ
Cybulsky
M I
MI
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*
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