Original Article

Chemoattractants Induce a Rapid and Transient Upregulation of Monocyte 4 Integrin Affinity for Vascular Cell Adhesion Molecule 1 Which Mediates Arrest: An Early Step in the Process of Emigration

Correspondence to: Myron I. Cybulsky, Toronto General Research Institute, 200 Elizabeth St., CCRW 1-855, Toronto, Ontario, Canada M5G 2C4. Tel:416-340-3578 Fax:416-340-3578 E-mail:myron.cybulsky{at}utoronto.ca.

Chemoattractants and chemokines induce arrest of rolling monocytes during emigration from blood into tissues. In this study, we demonstrated that 4 integrin affinity for vascular cell adhesion molecule (VCAM)-1 was upregulated rapidly and transiently by chemoattractants and stromal cell–derived factor (SDF)-1 and mediated monocyte arrest. 4 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-1 treatment and declined after 2 min. In a parallel plate flow chamber assay, FP, C5a, platelet-activating factor, or SDF-1 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.

Key Words: stromal cell–derived factor 1, chemokines, formyl peptide, very late antigen 4, inflammation

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