The Journal of Experimental Medicine
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Published online 21 May 2001.
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© The Rockefeller University Press, 0022-1007/2001/5/1149/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 10, May 21, 2001 1149-1158

Original Article

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



Jason R. Chana, Sharon J. Hyduka, and Myron I. Cybulskya

a Department of Laboratory Medicine and Pathobiology, University of Toronto and Toronto General Research Institute, Toronto, Ontario, Canada M5G 2C4
Toronto General Research Institute, 200 Elizabeth St., CCRW 1-855, Toronto, Ontario, Canada M5G 2C4.416-340-3578416-340-3578

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 {alpha}4 integrin affinity for vascular cell adhesion molecule (VCAM)-1 was upregulated rapidly and transiently by chemoattractants and stromal cell–derived factor (SDF)-1{alpha} and mediated monocyte arrest. {alpha}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{alpha} treatment and declined after 2 min. In a parallel plate flow chamber assay, FP, C5a, platelet-activating factor, or SDF-1{alpha} 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{alpha} • chemokines • formyl peptide • very late antigen 4 • inflammation

Abbreviations used in this paper: CXCR, CXC chemokine receptor; cytD, cytochalasin D; FBS, fetal bovine serum; FP, formyl peptide; ICAM, intercellular adhesion molecule; MCP, monocyte chemotactic protein; PAF, platelet-activating factor; PTx, pertussis toxin; RANTES, regulated upon activation, normal T cell expressed and secreted; SDF, stromal cell–derived factor; VCAM, vascular cell adhesion molecule.

© 2001 The Rockefeller University Press


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