Chemoattractants induce a rapid and transient upregulation of monocyte alpha 4 integrin affinity for vascular cell adhesion molecule 1 which mediatesarrest: An early step in the process of emigration

Chemoattractants and chemokines induce arrest of rolling monocytes during e migration from blood into tissues. In this study, we demonstrated that alph a4 integrin affinity for vascular cell adhesion molecule (VCAM)-1 was upreg ulated rapidly and transiently by chemoattractants and stromal cell-derived factor (SDF)-1 alpha and mediated monocyte arrest. alpha4 integrin affinit y changes were detected and blocked using soluble VCAM-1/Fc (sVCAM-1/Fc). I n a now cytometry assay, markedly increased sVCAM-1/Fc binding to human blo od monocytes or U937 cells transfected with formyl peptide (FP) receptor wa s detected 30 s after FP or SDF-1 alpha treatment and declined after 2 min. In a parallel plate flow chamber assay, FP, C5a, platelet-activating facto r, or SDF-1 alpha coimmobilized with VCAM-1 induced leukocyte arrest, which was blocked by inclusion of sVCAM-1/Fc but not soluble nonimmune immunoglo bulin G in the assay buffer.